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Se presenta un niño de 6 años con antecedente de retraso del lenguaje que llevó a sus padres a realizar múltiples consultas. En un primer momento, su cuadro fue interpretado como parte de un retraso global del desarrollo. Posteriormente, el paciente presentó convulsiones y episodios de descompensación metabólica, comenzando desde entonces su seguimiento por los Servicios de neurología, genética y metabolismo. Finalmente, tras varios estudios complementarios, por medio de un exoma trío se arribó al diagnóstico de síndrome de microduplicación del cromosoma 7q11.23, lo que justifica tanto el retraso global de desarrollo del paciente como su clínica neurológica. (AU)
A six-year-old boy presents with a history of language delay that led his parents to make multiple consultations. At first, we interpreted his condition as part of a global developmental delay. Subsequently, the patient presented seizures and episodes of metabolic decompensation, and since then, he had to be followed up by neurology, genetics, and metabolism services. Finally, after several complementary studies, following a trio exome analysis, we diagnosed chromosome 7q11.23 microduplication syndrome, which explains his global developmental delay and neurological symptoms. (AU)
Subject(s)
Humans , Male , Child , Chromosomes, Human, Pair 7/genetics , Developmental Disabilities/genetics , Williams Syndrome/genetics , Chromosome Duplication , Language Development Disorders/genetics , Intellectual Disability/genetics , Developmental Disabilities/diagnosis , Developmental Disabilities/metabolism , Genetic Testing , Williams Syndrome/diagnosis , Williams Syndrome/metabolism , Language Development Disorders/diagnosis , Intellectual Disability/diagnosis , Intellectual Disability/metabolismABSTRACT
INTRODUCTION: Hemophagocytic syndrome results from hyperactivity of histiocytes and lymphocytes, triggered by infections, mainly viral by cytomegalovirus, Epstein-Barr and herpes. Fanconi anemia (FA) is a rare genetic disease with heterogeneous symptoms common to other diseases such as VACTERL, a disease of unknown etiology in which there are several congenital malformations. The concomitance of Fanconi and VACTERL anemia occurs in 5 to 30% of FA patients. REPORT: A 14-month-old male infant was admitted to investigate fever, hepatosplenomegaly, and granulopenia. The patient was diagnosed with hemophagocytic syndrome due to hyperferritinemia, bone marrow hemophagocytosis, transaminase elevation, decreased fibrinogen, and cytomegalovirus (CMV) infection confirmed by serology and PCR. The test with mitomycin C (MMC) showed chromosomal fragility. The patient was diagnosed with a VACTERL/FA association for having a clinic and a test compatible with both FA and VACTERL. CONCLUSION: The VACTERL/FA association is seldom described, but is present in pediatric medical practice. This study presented the main clinical-laboratory aspects and reviewed the main aspects of the concurrence of this pathology.
INTRODUÇÃO: A síndrome hemofagocítica decorre da hiperatividade de histiócitos e linfócitos e é desencadeada por infeções, principalmente virais por citomegalovírus, Epstein-barr e herpes. A anemia de Fanconi (AF) é uma doença genética rara com sintomas heterogêneos em comum a outras doenças como a associação VACTERL, uma doença de etiologia desconhecida na qual existe diversas mal formações congênitas. A concomitância da anemia de Fanconi e VACTERL é descrita em 5 a 30% dos pacientes AF. RELATO: Lactente de 14 meses, sexo masculino, admitido para investigar um quadro de febre, hepatoesplenomegalia e granulopenia. Os exames laboratoriais mostraram a hiperferritemia, elevação da transaminases, medula óssea com hemofagocitose e, sorologia e PCR positivos para citomegalovírus (CMV). O paciente foi diagnosticado com síndrome hemofagocítica por citomegalovírus. Como havia também hipoplasia do polegar esquerdo, presença de hemivértebra, agenesia renal e teste positivo de fragilidades cromossômicas com mitomicina C (MMC), o paciente foi diagnosticado com associação VACTERL/AF. CONCLUSÃO: O citomegalovírus quando infecta pacientes com problemas de imunidade como AF, apresenta risco de desencadear a síndrome hemofagocítica. A associação VACTERL/AF é pouco descrita, mas presente na prática médica da pediatria. Esse estudo descreveu os principais aspectos clínicos-laboratoriais e revisou os aspectos fundamenais descritos sobre a concomitância dessas patologias.
Subject(s)
Humans , Male , Infant , Congenital Abnormalities , Lymphohistiocytosis, Hemophagocytic , Fanconi Anemia , Chromosome Fragility , Cytomegalovirus Infections , Rare DiseasesABSTRACT
El Fósforo es regulado por el riñón y el sistema óseo orquestado principalmente por la acción de la parathormona (PTH) y una molécula recientemente descrita como el factor de crecimiento fibroblástico 23 (FGF-23) . Presentamos los casos de dos pacientes madre-hijo con Raquitismo hipofosfatémico ligado al cromosoma X. Se realizó el estudio genético identificándose una mutación en el Gen PHEX: variante patogénica tipo splicing en hemicigosis: mutación previamente descrita como HGMD CS126536. El Raquitismo Hipofosfatémico forma parte de un grupo de tubulopatías caracterizadas hiperfosfaturia. La mutación del gen PHEX con pérdida de función conduce al aumento de FGF-23. PHEX degrada el FGF-23 en fragmentos inactivos, evitando la excreción excesiva de fosfatos y el desarrollo de hipofosfatemia. En un paciente con hipofosfatemia no dependiente de la hormona PTH o de la vitamina D y de presentación familiar debe considerarse el diagnóstico de Raquitismo hipofosfatémico ligado al cromosoma X.
Phosphate is regulated by the kidneys and the osseus system, mainly due to the action of parathyroid hormone (PTH) and a recently described molecule, fibroblast growth factor 23 (FGF-23). We present the cases of two patients, mother and son with X-chromosome linked hypophosphatemic rickets. The genetic study was performed, and a mutation in the PHEX gene was identified, a splicing type pathogenic variant in hemizygosis. This mutation was previously described as HGMD CS126536. Hypophosphatemic rickets belongs to a group of tubulopathies characterized by hyperphosphaturia. PHEX gene mutation with function loss leads to increased FGF-23 levels. PHEX degrades FGF-23 into inactive fragments, preventing excessive phosphate excretion and the development of hypophosphatemia. In patients with PTH or vitamin D non- dependent hypophosphatemia, a diagnosis of X-chromosome linked hypophosphatemic rickets should be considered.
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@#<b>Objective</b> To investigate the occupational health status of 450 radiation workers in a steel mill when they resigned, and to provide references and suggestions for the occupational health monitoring of the enterprise employees and for the workers’ proper arrangement after their resignations. <b>Methods</b> Occupational health examinations were performedon 450 steel workers who were about to resign in accordance with the applicable laws and regulations. And the examination results were statistically analyzed. <b>Results</b> Among the 450 radiation workers, 82% had abnormal examination results which included chromosome aberration in peripheral blood lymphocytes (4.89%), lens opacity (44.44%), pinguecula (25.33%), hypertension (28.22%), thyroid dysfunction (9.59%), and abnormal liver ultrasound findings (30.89%). Compared with the normal population, these steel workers had a significantly higher chromosome aberration rate in peripheral blood lymphocytes and a significantly higher incidence rate of ocular disorders. <b>Conclusion</b> It is important to effectively manage the occupational health of radiation employees in steel mills, and to regularly provide training on occupational health protection. To avoid radiation damage, workers should pay close attention to radiation protection at work, especially eye protection, to avoid eye disorders.
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OBJECTIVES@#To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage.@*METHODS@#Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed.@*RESULTS@#Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6.@*CONCLUSIONS@#Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.
Subject(s)
Male , Humans , Haplotypes , Chromosomes, Human, Y/genetics , Microsatellite Repeats , Mutation , Asian People/genetics , China , Genetics, PopulationABSTRACT
Objective Primary ovarian small cell carcinoma of pulmonary type (SCCOPT) is a rare ovarian tumor with a poor prognosis. The platinum-based chemotherapy is the standard treatment. However, there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence. The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical, imaging, laboratorical and pathological characteristics of 37 SCCOPT cases, in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases (n=37) was 56.00 (range, 22-80) years. Almost 80% of them had a stage Ⅲ or Ⅳ tumor. All patients underwent an operation and postoperative chemotherapy. Nevertheless, all cases had a poor prognosis, with a median overall survival time of 12 months. Immunohistochemically, the SCCOPT of all patients showed positive expressions of epithelial markers, such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2 (SOX-2), and negative expressions of estrogen receptor, progesterone receptor, vimentin, Leu-7, and somatostatin receptor 2. The tumor of above 80% cases expressed synaptophysin. Only a few cases expressed neuron-specific enolase, chromogranin A, and thyroid transcription factor-1. Conclusions SCCOPT had a poor prognosis. SOX-2 could be a biomarker to be used to diagnose SCCOPT.
Subject(s)
Female , Humans , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Carcinoma, Small Cell/pathology , Carcinoma, Ovarian Epithelial , Ovarian Neoplasms/therapy , PrognosisABSTRACT
Introdução: As deleções intersticiais envolvendo a região 2q31q32 são reconhecidas como um transtorno clínico, envolvendo diversas manifestações como deficiência intelectual, retardo no crescimento, distúrbios comportamentais e dismorfologias faciais. Os números reduzidos de relatos de pacientes acometidos por essa síndrome contribui para que as correlações genótipos-fenótipos sejam difíceis de se fazer. Relato de caso: Paciente com inversão do braço longo do cromossomo 2 [46, XX,inv(2)(q21q33)]. Apresentou ao exame físico dismorfológico fronte proeminente, epicanto, ponte nasal baixa, filtro nasolabial longo e lábio superior fino. Ao exame neurológico, apresentava hipotonia. Discussão: Uma correta interpretação cromossômica pode não só identificar a síndrome de microdeleção como também, descartar ou confirmar possíveis diagnósticos diferenciais, deixando evidente a necessidade e a importância de se reconhecer e documentar os casos (AU).
Introduction: Interstitial deletions involving the 2q31q32 region are recognized as a clinical disorder involving several manifestations, such as intellectual disability, growth retardation, behavioral disorders, and facial dysmorphologies. The reduced number of reports of patients affected by this syndrome contributes to the difficulty of making genotype-phenotype correlations. Case report: Patient with inversion of the long arm of chromosome 2 [46, XX,inv(2)(q21q33)]. On physical examination, he had a prominent forehead, epicanthus, low nasal bridge, long nasolabial philtrum and thin upper lip. Neurological examination showed hypotonia. Discussion: A correct chromosomal interpretation can identify the microdeletion syndrome and rule out or confirm possible differential diagnoses, highlighting the need and importance of recognizing and documenting cases (AU).
Subject(s)
Humans , Female , Infant , Chromosome DeletionABSTRACT
ABSTRACT Objective: To evaluate radiological (gestational and perinatal) and neonatal signs of patients with Patau syndrome and semilobar holoprosencephaly, as well as to report the association of both pathologies. Case description: This case report is about a female infant, born at term with trisomy of the chromosome 13 and semilobar holoprosencephaly, with thalamic fusion and a single cerebral ventricle, in addition to several other changes that worsened the patient's prognosis. Comments: Chromosome 13 trisomy is a genetic alteration that leads to the symptoms that determines Patau syndrome. In this syndrome, cardiovascular, urogenital, central nervous system, facial structure and intellectual impairment are common, in addition to problems in limb formation, such as decreased humerus and femur length, polydactyly, hypotelorism and low ear implantation. It is estimated, however, that holoprosencephaly is present in only 24 to 45% of the patients with trisomy 13.
RESUMO Objetivo: Avaliar sinais radiológicos (gestacionais e perinatais) e neonatais de paciente com síndrome de Patau e holoprosencefalia semilobar, assim como relatar a associação de ambas as patologias. Descrição do caso: Trata-se de um relato de recém-nascido do sexo feminino a termo, que apresentou trissomia do cromossomo 13 e holoprosencefalia semilobar, com fusão talâmica e ventrículo cerebral único, além de várias outras alterações que pioraram o prognóstico da paciente. Comentários: A trissomia do cromossomo 13 é um defeito genético que caracteriza um conjunto de sintomas que compõem a Síndrome de Patau. Nesta síndrome, é comum o acometimento cardiovascular, urogenital, do sistema nervoso central, da estrutura facial e da capacidade intelectual, além de falhas na formação dos membros, como diminuição no comprimento do úmero, fêmur, polidactilia, hipotelorismo e baixa implantação das orelhas. Estima-se, no entanto, que a holoprosencefalia apresente-se nesse grupo de malformações congênitas apenas em 24 a 45% dos casos.
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@#Objective Genetic analysis was performed on a female child with chromosome Xq28 heterozygous deletion and suspected X-linked recessive disease to determine the morbidity and prognosis. Methods A female child was admitted to the hospital on day 20 because of "jaundice for 20 days and difficulty in stopping bleeding at acupuncture sites". Low depth whole genome test of amniocentesis in late pregnancy suggested missing copy number of hemophilia A and X-linked mental retardation type 72. In order to further confirm the diagnosis and prognosis, peripheral blood of the children and their parents were collected for gene testing, chromosome inactivation test and genetic analysis. Results Chromosome Xq28 of the child had 439.4 kb copy number heterozygous deletion variation, which was a clear disease-coding gene for functional loss included in ClinGen database. Chromosome inactivation test showed that the paternal X chromosome of the child was extremely inactivated. Haplotype analysis suggested that the normal chromosome of the subject was inherited from the mother, and there was heterozygous deletion on the paternal X chromosome, so it was inferred that the child will not develop disease or just have mild symptoms. Conclusion It is necessary to analyze the X chromosome inactivation test for female patients with the pathogenic variation of X-linked recessive genetic disease to determine the possibility of the disease.
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@#<b>Objective</b> To investigate the changes of chromosome aberration and micronucleus frequencies in the peripheral blood of patients with cancer before and after treatment, and to provide a basis for clinical prevention and treatment. <b>Methods</b> We collected the physical examination data of 102 patients with cancer before and after treatment from 2016 to 2021 to analyze the changes of chromosome aberration and micronucleus frequencies in peripheral blood. <b>Results</b> Before and after treatment, there were significant differences in chromosome aberration frequency and micronucleus frequency in peripheral blood lymphocytes in patients having radiotherapy or chemoradiotherapy (all <i>P</i> < 0.05), but no significant difference was observed in either index for patients having chemotherapy (both <i>P</i> > 0.05). Before and after radiotherapy, there were significant differences in the numbers of patients with abnormal chromosome aberration frequency and those with abnormal micronucleus frequency in lymphocytes (both <i>P</i> < 0.001). Before and after chemotherapy, there was no significant difference in the number of patients with abnormal chromosome aberration frequency (<i>P</i> = 0.100) or those with abnormal micronucleus frequency (<i>P</i> = 0.110). <b>Conclusion</b> Radiotherapy can cause abnormalities in chromosome aberration and micronucleus frequencies in peripheral blood lymphocytes, which can be useful for monitoring radiotherapy injury to formulate effective emergency plans and evaluate radiation dose in each course of treatment.
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Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.
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Objective:To investigate the clinical value of isolated fetal echogenic bowel (FEB) as an indicator for invasive prenatal diagnosis.Methods:This retrospective study enrolled 183 pregnant women who were diagnosed with isolated FEB and underwent invasive prenatal diagnosis in Fujian Maternity and Child Health Hospital from August 2013 to January 2021. Clinical data including the results of conventional karyotyping and chromosomal microarray analysis (CMA), cytomegalovirus (CMV) DNA loads in amniotic fluid and pregnancy outcomes were reviewed analyzed. Chi-square test was used for statistical analysis Results:Karyotyping was performed on all of the 183 fetuses and three (1.64%) aneuploidies (one case of trisomy 21, one trisomy 18 and one 47,XYY syndrome) were detected. One trisomy 21 and four pathogenic (P)/likely pathogenic (LP) copy number variation (CNV) were detected among 108 fetuses who received CMA. The detection rate of P/LP chromosomal abnormalities by CMA was higher than that by karyotyping, but there was no significant difference between them [4.63% (5/108) vs 0.93% (1/108), χ 2=1.54, P>0.05]. In addition, three cases of variants of uncertain significance (VOUS) were detected by CMA. CMV DNA loads of fetal cells in the amniotic fluid samples of the 166 cases were determined, and only one (0.6%) was positive (CMV DNA up to 7.01×10 6 copies/ml), and no abnormalities were found in karyotype analysis and CMA detection. A total of 176 cases were followed up, and among them only one case of intrauterine infection and seven cases (three aneuploidies and four P/LP CNV) of chromosomal abnormalities were terminated after genetic counseling. Three fetuses with VOUS and other 165 fetuses without chromosomal abnormalities had a good prognosis after birth. Conclusions:Isolated FEB may be the abnormal ultrasound finding in fetuses with chromosomal abnormalities or CMV infection. Prenatal genetic testing and the exclusion of intrauterine infection are important for management during pregnancy and prognosis assessment of FEB.
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Objective:To investigate the performance of chromosome karyotype, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) in prenatal diagnosis of true fetal chromosome mosaicism. Methods:This retrospective study enrolled 40 women with true fetal chromosome mosaicism from 4 071 singleton pregnant women who were indicated for and underwent amniocentesis or/and cordocentesis in the the First Affiliated Hospital of Sun Yat-sen University from April 2018 to August 2021. The results of chromosome karyotyping, CMA and FISH, the types of chromosomal mosaicism, mosaicism ratio and pregnancy outcomes were analyzed using Chi-square test. Results:(1) The detection rate of true fetal mosaicism was 0.98% (40/4 071). (2) Sex chromosome mosaicism accounted for 42.5% (17/40). Other chromosomal mosaicism involved chromosomes 21, 22, 18, 16, 7, 12, 15, 17 and 20, as well as balanced chromosomal translocation. (3) The detection rate of true fetal mosaicism by chromosome karyotyping was 77.4% (24/31) from amniotic fluid samples and 10/19 from umbilical cord blood samples, while that data by CMA was 76.7% (23/30) and 7/11,respectively. (4) Of the 40 pregnant women with fetal chromosome mosaicism, FISH test was performed on 20 cases (14 cases were verified with both amniotic fluid and umbilical cord blood samples, five with amniotic fluid samples and one with umbilical cord blood sample), and all of the diagnosis of mosaicism were confirmed. For those with mosaicism ratio <30%, the detection rate by FISH was higher than that by CMA among amniotic fluid samples [14/19 vs 43.5% (10/23), χ2=3.88, P=0.049]. (5) Among the 40 pregnant women, five were lost to follow-up; 18 chose to terminate the pregnancy; and 17 continued the pregnancy to delivery. No abnormalities in mental or physical development were reported in the 17 neonates after birth or during on-line follow-up between 6 to 24 months old. Of the 14 pregnant women with mosaicism ratio <30% which confirmed by FISH, eight chose to continue the pregnancy, and no abnormalities in mental development or growth were found in the neonates. Conclusions:In prenatal diagnosis of true fetal choromosome mosaicism, the incidence of sex chromosome mosaicism is the highest. FISH may improve the prenatal diagnosis rate of mosaicism and is more accurate in determining the mosaicism ratio. The combination of FISH, CMA and chromosome karyotyping would significantly improve the detection rate of chromosomal mosaicism and assess the mosaicism ratio more accurately, which is of great value in clinical consultation and evaluation of fetal prognosis.
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Objective:To analyze the prenatal clinical phenotypes and pregnancy outcomes of fetuses with 22q11.21 microdeletion and microduplication syndrome to provide a basis for clinical genetic counseling.Methods:This retrospective study involved the cases diagnosed with 22q11.21 microdeletion or microduplication by chromosomal microarray analysis (CMA) due to abnormal ultrasound findings, advanced maternal age, or high-risk pregnancies indicated by serum screening in the Prenatal Diagnosis Center of the First Affiliated Hospital of Air Force Medical University from January 2015 to January 2022. Clinical phenotypes and pregnancy outcomes of the fetuses were analyzed and described.Results:Among 9 141 cases referred for CMA during the study period, 77 cases (0.8%) were diagnosed as 22q11.21 microdeletion or microduplication, including 62 (80.5%) with 22q11.21 microdeletion and 15 (19.5%) with microduplication. In the 22q11.21 microdeletion cases, 58 had typical deletion, and four had atypical deletions, but all fetuses carried TBX1 gene that was clearly associated with congenital heart disease. The 15 fetuses with 22q11.21 microduplication including 14 in the typical region and one in the atypical region. Forty-eight (77.4%) out of the 62 fetuses with 22q11.21 microdeletion were complicated by congenital heart defects, including 28 with conotruncal defects. Five of the 15 fetuses with 22q11.21 microduplication were complicated by congenital heart defects. The cases were followed up on telephone at three to six months after the expected date of delivery. Among the 62 cases with 22q11.21 microdeletion, 52 terminated pregnancies, five were lost to follow-up, and five were delivered (one died after one month of premature delivery, one was born with anal advancement and growth retardation, and three were followed up without obvious abnormality). Among the 15 cases with 22q11.21 microduplication, four terminated pregnancies, two were lost to follow-up, and nine gave birth (eight were followed up without obvious abnormality, one grew slowly). Conclusions:The application of CMA in the prenatal diagnosis of 22q11.21 microdeletion and microduplication fetuses, and the comprehensive analysis of clinical manifestations and pregnancy outcome combined with ultrasonic diagnosis are of great significance in guiding the treatment and rehabilitation after birth of an affected child. Genetic counseling for cases with 22q11.21 microdeletion and microduplication syndrome should be cautious and consider ultrasound findings.
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Objective:To investigate the prenatal ultrasonographic features and diagnosis of 16p12.2 copy number variation (CNV).Methods:This retrospective study recruited seven fetuses with 16p12.2 microdeletion/microduplication in the First Affiliated Hospital of Fujian Medical University from January 2017 to December 2021. Data, including the prenatal diagnostic indications, ultrasound findings, karyotypes, genetic testing and mutation tracing results, pregnancy outcomes, and postnatal follow-up data, were summarized with descriptive statistical analysis.Results:Prenatal ultrasound indicated three fetuses with structural abnormalities, including one case each of multiple malformations, interventricular septal defect, and cleft lip and palate. The other four cases were positive for ultrasonic soft markers involving the heart and kidney. The chromosome karyotypes of the seven fetuses were normal. Single nucleotide polymorphism array (SNP array) results showed that four cases had a 381.7-542.4 kb microdeletion containing three genes ( OTOA, METTL9, and IGSF6) in Online Mendelian Inheritance in Man (OMIM) at 16p12.2 (distal region) and three cases had a 484.0-701.7 kb microdeletion/microduplication containing four OMIM genes ( UQCRC2, CDR2, EEF2K, and POLR3E) at 16p12.2 (proximal region). Five (cases 1, 2, 4, 5, and 6) out of the seven fetuses inherited the variants from their phenotypically normal mother/father, and among them, three (cases 2, 4, and 5) were delivered at term and healthy. Two cases (cases 3 and 7) refused to undergo pedigree verification. Case 3, a full-term infant, underwent ventricular septal defect repair three months after birth, and no abnormality was found at 18 months of age. Conclusions:No specific phenotype presents in fetuses with 16p12.2 microdeletion/microduplication in prenatal diagnosis. OTOA gene is the key gene associated with abnormality in the distal region of 16p12.2. Pedigree analysis is conducive to preventing unnecessary termination of pregnancy.
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Objective:To analyze the genetic etiology and prognosis in fetuses with increased nuchal translucency (NT) in order to assist in the clinical prenatal genetic counseling and diagnosis.Methods:This study retrospectively enrolled 1 658 cases of singleton pregnancy (<35 years old) receiving invasive prenatal diagnosis, including karyotype analysis and/or chromosome microarray analysis or copy number variation (CNV) sequencing, due to NT value ≥2.5 mm in the first trimester in Henan Provincial People's Hospital from August 2014 to December 2021. They were divided into different groups according to the thickness of NT (≥2.5-<3.0, ≥3.0-<3.5, ≥3.5-<4.5, ≥4.5-<5.5, ≥5.5-<6.5 and ≥6.5 mm groups) and abnormal ultrasound findings (isolated increased NT group, increased NT complicated by soft markers/non-severe structural abnormality group and increased NT complicated by severe structural abnormality group). The results of invasive prenatal diagnosis and pregnancy outcomes were compared between different groups using Chi-square test and trend Chi-square test. Results:The detection rates of numerical abnormalities of chromosomes were 15.8% (262/1 658) and 17.6% (252/1 431) when the NT thickness cut-off value were 2.5 mm or 3.0 mm, respectively. Overall, the detection rate of numerical abnormalities of chromosomes increased with thickness of NT ( χ2trend=180.75, P<0.001), ranging from 6.6% (44/671) in the NT≥2.5-<3.5 mm group to 45.6% (113/248) in the NT≥5.5 mm group. The incidence of pathogenic/likely pathogenic CNV(P/LP CNV) did not increased with NT thickness ( χ2trend=3.26, P=0.071), and the highest detection rate was observed in the NT≥4.5-<5.5 mm group (9.0%, 19/211). The detection rate of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥2.5-<3.0 mm group and NT≥3.0-<3.5 mm group were 5.3% (10/188) and 9.6% (36/375), respectively, however, the difference was not statistically significant ( χ2=3.06, P=0.080). The detection rates of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥3.5-<4.5 mm group and NT≥2.5-<3.0 mm complicated by soft markers/ non-severe structural abnormality group were 12.7% (52/410) and 24.1% (7/29), respectively, and the risk were 2.6 times (95% CI: 1.3-5.2) and 5.7 times (95% CI: 2.0-16.4) of the isolated NT≥2.5-<3.0 mm group, respectively. The pregnancy termination rate increased with the NT thickness ( χ2trend=304.42, P<0.001), ranging from 10.8% (23/212) in the NT≥2.5-<3.0 mm group to 90.7% (117/129) in the NT≥6.5 mm group. After exclusion of the pregnancies terminated due to numerical abnormalities of chromosomes and P/LP CNV, 87.6% (862/984) of the fetus with increased NT were born alive. Conclusions:The detection rate of numerical abnormalities of chromosomes increases with the thickness of NT. Invasive prenatal diagnosis is required for non-advance aged singleton pregnant women when fetuses present with isolated NT≥2.5 mm with or without soft markers/structural abnormalities.
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Objective:To analyze the clinical and genetic features of the children with 5p15.1-5p15.33 duplication at the end of the short arm of chromosome 5 (5p).Methods:Clinical data of a 5p15.1-5p15.33 duplicative patient diagnosed in the Department of Pediatric Intensive Care Unit of West China Second University Hospital of Sichuan University in July 2021 were collected, and the characteristics of the patients of 5p duplication syndrome reported in the literatures were summarized and analyzed.Results:The boy was 1 year and 5 months old at the time of admission. The main clinical manifestations included growth restriction and developmental delay after birth, accompanied by craniofacial deformities. At 7 months old, he was diagnosed as epilepsy due to convulsive limbs. At present, he is 2 years old, still has recurrent convulsions, can not raise his head, sit alone, crawl and talk, with hypotonia. Repeated cranial magnetic resonance imaging showed agenesis of the corpus callosum. The child′s parents had normal phenotypes. His copy number variation sequencing results showed partial overlap of chromosome 5p15.1-5p15.33 (chr5:1934522-18905656), which was determined as pathogenic copy number variation according to copy number variations evaluation criteria, and no abnormality was detected in his parents. According to the retrieval strategy set in this study, 10 literatures (all in English, reporting 17 cases) were retrieved, and a total of 22 5p duplication syndrome patients (including this case and 4 cases included in databases) were included. Seventeen of the 22 patients were younger than 14 years old with a onset age of 7 (0, 18) years, and the male to female ratio was about 1.1∶1. Among the 22 patients, craniofacial malformation was found in 19 patients, developmental disorder in 18, bone/muscle dysplasia in 15, autism in 11, attention deficit hyperactivity disorder in 9, mental retardation in 8, obesity in 5, epilepsy in 5, congenital heart dysplasia in 2, hypotonia in 4, strabismus/hyperopia in 2, and corpus callosum dysplasia, endocrine dysfunction, inguinal hernia as well as umbilical hernia in 1, respectively. There were 19 cases of multiple malformation and 3 cases of single malformation.Conclusions:5p15.1-5p15.33 duplication may be the genetic cause of this child. Facial malformation, developmental delay, skeletal/muscular dysplasia, intellectual disability, autism spectrum disorder and attention deficit hyperactivity disorder are the main clinical phenotypes of 5p copy number duplication. Corpus callosum dysplasia may be an extended phenotype of chromosome duplication at this location.
ABSTRACT
La duplicación en el brazo largo del cromosoma 10 (10q) es una cromosomopatía poco frecuente caracterizada clínicamente por retraso en el crecimiento prenatal y postnatal asociado a hipotonía, retraso en el desarrollo y hallazgos faciales específicos; que representa un reto diagnóstico en el ámbito clínico. Se presenta el caso de una recién nacida remitida para valoración multidisciplinara al Hospital Universitario San Ignacio en Bogotá, Colombia; en quien se documentó al momento del nacimiento fisura de labio y paladar, hipertelorismo, pabellón auricular con implantación baja e hipertrofia de labios menores. Se realizó resonancia magnética cerebral, la cual reportó pequeños quistes connatales adyacentes a las astas frontales de los ventrículos laterales, sin significado patológico, aparente malrotación de ambos hipocampos, hipertelorismo y queilopalatosquisis bilateral. El reporte del cariotipo con bandeo G confirmó complemento cromosómico 46,XX,dup(10)(q23q24); siendo el primer caso reportado en Colombia.
Duplication on the long arm of chromosome 10 (10q) is a rare chromosomopathy characterized clinically by delayed prenatal and postnatal growth associated with hypotonia, delayed development, and specific facial findings, which represents a diagnostic challenge in the clinical setting. We present the case of a newborn referred for multidisciplinary evaluation at the Hospital Universitario San Ignacio in Bogotá, Colombia; in whom cleft lip and palate, hypertelorism, low-set auricle and hypertrophy of the labia minora were documented at birth. Magnetic resonance imaging of the brain was performed, which reported small connatal cysts adjacent to the frontal horns of the lateral ventricles, without pathological significance, apparent malrotation of both hippocampi, hypertelorism, and bilateral cheilopalatoschisis. The G-band karyotype report confirmed chromosomal complement 46, XX, dup (10) (q23q24); being the first reported case in Colombia.
ABSTRACT
Introduction: Ectodermal dysplasia is a rare genetic disorder that affects structures derived from ectoderm such as teeth, hair, nails, and sweat glands. Oligodontia is a common finding that affects the chewing, smiling and self- esteem of these pediatric patients. Case Report: We present a case report of a 7-years-old pediatric patient who consulted with his mother, showing the same condition. The intervention consisted of a removable prosthesis with satisfactory results. Conclusion: The X-linked hypohidrotic ectodermal dysplasia represents a challenge for a pediatric dentist who offers rehabilitation to the patient according to craniofacial development, age, socioeconomic status, and the number of missing teeth.
Introducción: La oligodoncia es un hallazgo común que afecta la masticación, la sonrisa y la autoestima de estos pacientes pediátricos. Case Report: Presentamos un reporte de caso de un paciente pediátrico de 7 años que consultó con su madre presentando la misma condición. La intervención consistió en una prótesis de remoción con resultados satisfactorios. Conclusión: La displasia ectodérmica hipohidrótica ligada al cromosoma X representa un desafío para un odontopediatra que ofrece rehabilitación al paciente de acuerdo con el desarrollo craneofacial, la edad, el nivel socioeconómico y el número de dientes faltantes.
Subject(s)
Humans , Male , Child , Tooth Abnormalities/therapy , Dental Prosthesis/methods , Ectodermal Dysplasia 1, Anhidrotic/therapy , Anodontia/therapy , Quality of Life , Treatment Outcome , Denture, Partial, RemovableABSTRACT
ABSTRACT Chile is located in the south-western region of South America along the Pacific Ocean and contributes to the worldwide flora with ca. 6,120 species of Bryophyta, Pteridophyta, Pinophyta, Gnetophyta, and Magnoliophyta (1.9% of worldwide total species), exhibiting high endemism across all plant divisions. Little is known about the genetic diversity of Chilean land plants worldwide, including their cytogenetic and molecular characteristics. In 2012 we published the first state-of-the-art review in Cytogenetics of Chilean Angiosperms. The article gathered 78 publications from 1924 to 2010 accounting for approximately 139 species (2.8% of total Chilean species). The aim of this paper was to review the advances in cytogenetic studies of Chilean land plants, reporting additional cytogenetic data for species of four botanical divisions until 2020. Cytogenetic data were searched in the CPCD (Chilean Plants Cytogenetic Database). In total, we found 180 publications from both Chilean and foreign researchers. To date, cytogenetic data have been reported for 499 Chilean land plant species (8.2% of total) belonging to 244 genera and 117 families. In this context, the 2001-2020 period has been among the most productive regarding publications, with 74 available reports that include 163 additional species. Based on chromosome numbers, angiosperms and bryophytes registered the greatest diversity with 55 and 29 different 2n, respectively; both divisions having the greatest number of studied species. Given the importance of increasing information on Chilean land plants, it is expected that more publications will contribute to the knowledge of their cytogenetic diversity in the near future.
RESUMEN Chile está ubicado en la región suroeste de América del Sur a lo largo del Océano Pacífico y contribuye a la flora mundial con aproximadamente 6.120 especies de Bryophyta, Pteridophyta, Pinophyta, Gnetophyta y Magnoliophyta (1,9% del total de especies en todo el mundo), que presentan un alto endemismo en todas las divisiones de plantas. Poco se conoce sobre la diversidad genética de las plantas terrestres chilenas en todo el mundo, incluidas sus características citogenéticas y moleculares. En 2012 publicamos la primera revisión sobre el estado del arte en Citogenética de Angiospermas Chilenas. El artículo reunió 78 publicaciones desde 1924 hasta 2010, que representan aproximadamente 139 especies (2,8% del total de especies chilenas). El objetivo de este trabajo fue revisar los avances en estudios citogenéticos de plantas terrestres chilenas, reportando datos citogenéticos adicionales para especies de cuatro divisiones botánicas hasta el 2020. Los datos citogenéticos se buscaron en el CPCD (Base de Datos Citogenéticos de Plantas Chilenas). En total, encontramos 180 publicaciones sobre citogenética de plantas terrestres chilenas, con datos citogenéticos para 499 especies (8,2% del total) pertenecientes a 244 géneros y 117 familias. En este contexto, el período 2001-2020 ha sido uno de los más productivos en cuanto a publicaciones, con 74 artículos disponibles que incluyen 163 especies adicionales. Basado en los números cromosómicos, angiospermas y briófitos registran la mayor diversidad, con 55 y 29 2n diferentes, respectivamente; ambas divisiones tienen también el mayor número de especies estudiadas. Dada la importancia de incrementar la información sobre plantas terrestres chilenas, se espera que más publicaciones contribuyan al conocimiento de su diversidad citogenética en un futuro próximo.