Genetic analysis of the false positive trisomy 7 and false negative trisomy 18 by NIPT-PLUS / 中华医学遗传学杂志

OBJECTIVE@#To explore the cause of inconsistency between the results of trisomy 7 by expanded non-invasive prenatal testing (NIPT-PLUS) and trisomy 18 by prenatal diagnosis.@*METHODS@#A pregnant woman who received genetic counseling at Jiaozuo Maternal and Child Health Care Hospital on July 5, 2020 was selected as the study subject. NIPT-PLUS, systematic ultrasound and interventional prenatal testing were carried out. The middle segment and root of umbilical cord, center and edge of the maternal and fatal surface of the placenta were sampled for the validation by copy number variation sequencing (CNV-seq).@*RESULTS@#The result of NIPT-PLUS indicated that the fetus has trisomy 7. Systematic ultrasound has shown multiple malformations including atrioventricular septal defect, horseshoe kidney, and rocker-bottom feet. However, QF-PCR, chromosomal karyotyping analysis, and CNV-seq of amniotic fluid samples all showed that the fetus was trisomy 18. Validation using multiple placental samples confirmed that the middle segment of the umbilical cord contains trisomy 18, the center of the placenta contained trisomy 7, and other placental sites were mosaicism for trisomy 7 and trisomy 18. Notably, the ratio of trisomy 18 became lower further away from the umbilical cord.@*CONCLUSION@#The false positive results of trisomy 7 and false negative trisomy 18 by NIPT-PLUS was probably due to the existence of placental mosaicism. Strict prenatal diagnosis is required needed aneuploidy is detected by NIPT-PLUS to exclude the influence of placental mosaicisms.

Avaliação e ensino de emoções com crianças e jovens adultos com autismo ou síndrome de down mediado pela família / Assessment and teaching of emotions with children and young adults with autism or down syndrome mediated by family / Evaluación y enseñanza de las emociones con niños y jóvenes con autismo o síndrome de down mediadas por la familia

Este estudo avaliou o reconhecimento (imitação, identidade e identificação) e a nomeação de estímulos emocionais de valência negativa (raiva e tristeza) e positiva (alegria e surpresa) em conjunto com a influência dos tipos de estímulos utilizados (social-feminino, social-masculino, familiar e emoji) em crianças e jovens adultos com autismo ou síndrome de Down, por meio de tarefas aplicadas pela família e mediadas por recursos tecnológicos durante a pandemia de covid-19. Participaram cinco crianças e dois jovens adultos com autismo e uma criança e dois jovens adultos com síndrome de Down. Foram implementadas tarefas de identidade, reconhecimento, nomeação e imitação, com estímulos faciais de função avaliativa (sem consequência diferencial) e de ensino (com consequência diferencial, uso de dicas e critério de aprendizagem), visando a emergência da nomeação emocional por meio do ensino das tarefas de reconhecimento. Os resultados da linha de base identificaram que, para os participantes que apresentaram menor tempo de resposta para o mesmo gênero, a diferença de tempo de resposta foi em média 57,28% menor. Em relação à valência emocional, 50% dos participantes apresentaram diferenças nos acertos, a depender da valência positiva e negativa, sendo que 66,66% apresentaram diferenças para o tempo de resposta a depender da valência emocional. Após o procedimento de ensino, os participantes mostraram maior número de acertos nas tarefas, independentemente do gênero de estímulo e valência emocional, criando ocasião para generalização da aprendizagem de reconhecimento e nomeação de emoções, além de consolidar a viabilidade de estratégias de ensino mediadas por recursos tecnológicos e aplicadas por familiares.(AU)

This study evaluated the recognition (imitation, identity, and identification) and naming of negative (anger and sadness) and positive (joy and surprise) emotional stimuli alongside the influence of the types of stimuli (social-female, social-male, family, and emoji) in children and young adults with autism and Down syndrome, via tasks applied by the family and mediated by technological resources, during the COVID-19 pandemic. Five children and two young adults with autism and one child and two young adults with Down syndrome participated. Identity, recognition, naming, and imitation tasks were planned and implemented using facial stimuli with evaluative (without differential consequence) and teaching (with differential consequence, tips, and learning criteria) functions, aiming at the emergence of emotional naming from the recognition teaching tasks. The baseline results showed that, for participants who had a shorter response time for the same gender, the response time difference was on average 57.28% lower. Regarding the emotional valence, 50% of the participants showed differences in the correct answers, depending on the positive and negative valence, and 66.66% showed differences in the response time depending on the emotional valence. After the teaching procedure, the participants showed a greater number of correct answers in the tasks, regardless of the stimulus type and emotional valence, creating an opportunity for generalizing learning of emotion recognition and naming, in addition to consolidating the feasibility of teaching strategies mediated by technological resources and applied by family members.(AU)

Este estudio evaluó el reconocimiento (imitación, identidad e identificación) y la denominación de estímulos emocionales negativos (enfado y tristeza) y positivos (alegría y sorpresa) y la influencia de los tipos de estímulos utilizados (social-femenino, social-masculino, familiar y emoji ) de niños y jóvenes con autismo o síndrome de Down, a través de tareas aplicadas por la familia, mediadas por recursos tecnológicos durante la pandemia de la covid-19. Participaron cinco niños y dos adultos jóvenes con autismo, y un niño y dos adultos jóvenes con síndrome de Down. Se planificaron e implementaron tareas de identidad, reconocimiento, nombramiento e imitación con estímulos faciales con función evaluativa (sin consecuencia diferencial) y enseñanza (con consecuencia diferencial, uso de ayudas y criterios de aprendizaje), buscando la emergencia del nombramiento emocional después de la enseñanza de tareas de reconocimiento. Los resultados de la línea de base identificaron que para los participantes que tenían un tiempo de respuesta más corto para el mismo género, la diferencia en el tiempo de respuesta fue un 57,28% menor. En cuanto a la valencia emocional, el 50% de los participantes mostraron diferencias en las respuestas correctas, en función de la valencia positiva y negativa, y el 66,66% tuvieron diferencias en el tiempo de respuesta, en función de la valencia emocional. Después del procedimiento de enseñanza, los participantes mostraron mayor número de aciertos en las tareas evaluadas, independientemente del tipo de estímulo o valencia emocional, lo que genera una oportunidad para la generalización del aprendizaje de reconocimiento y denominación de emociones, además de consolidar la viabilidad de estrategias de enseñanza mediadas por recursos tecnológicos y aplicadas por la familia.(AU)

Application value of CNV-seq for the prenatal diagnosis of women with high-risk pregnancies / 中华医学遗传学杂志

OBJECTIVE@#To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies.@*METHODS@#Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison.@*RESULTS@#The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05).@*CONCLUSION@#CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.

Expert consensus on the detection of genome-wide copy number variations in abortive tissues and family reproductive consultation / 中华医学遗传学杂志

Chromosomal aberrations including numerical abnormalities and segment duplications/deletions, as genome-wide copy number variations (CNVs), are a leading cause for spontaneous abortion. Analysis of abortive tissues for such CNVs can detect potential genomic variations in the couple and provide guidance for the choice of appropriate method to avoid further miscarriage or birth of child with chromosomal disorders. With evidence-based clinical data, an expert group jointly formed by the Genetic Disease Prevention and Control Group, Committee for Birth Defects Prevention and Control, Chinese Association of Preventive Medicine; the Clinical Genetics Group, the Society of Medical Genetics, Chinese Medical Association; the Professional Committee for Prenatal Diagnosis of Genetic Diseases, the Society of Medical Geneticists, Chinese Medical Doctor Association has discussed and formulated this consensus, with an aim to provide guidance for the application of genomic CNVs detection for the abortive tissue and genetic counseling for family reproduction.

Analysis of genetic etiology and related factors in 1 065 women with spontaneous abortions / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions.@*METHODS@#All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend.@*RESULTS@#Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05).@*CONCLUSION@#Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.

Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome.@*METHODS@#A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022.@*RESULTS@#For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes.@*CONCLUSION@#Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

The value of chromosomal microarray analysis and fluorescence in situ hybridization for the prenatal diagnosis of chromosomal mosaicisms / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms.@*METHODS@#A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases.@*RESULTS@#Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms).@*CONCLUSION@#For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.

Retrospective analysis of cell-free fetal DNA prenatal testing of maternal peripheral blood / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosome aneuploidies, chromosomal microdeletions and microduplications using cell-free fetal DNA from peripheral blood samples of pregnant women.@*METHODS@#A total of 15 237 pregnant women who had undergone NIPT testing at the Maternity and Child Health Care Hospital of Zaozhuang from February 2015 to December 2021 were enrolled in this study. For those with a high risk by NIPT, amniotic fluid samples were collected for G-banding chromosomal karyotyping analysis and chromosomal microarray analysis to verify the consistency of NIPT with results of prenatal diagnosis. All of the women were followed up by telephone for pregnancy outcomes.@*RESULTS@#Among the 15 237 pregnant women, 266 (1.75%) were detected with a high risk for fetal chromosomal abnormality were detected. Among these, 79 (29.7%) were at a high risk for T21, 26 (9.77%) were at a high risk for T18, 9 (3.38%) were at a high risk for T13, 74 (27.82%) were at a high risk for sex chromosome aneuploidies, 12 (4.51%) were at a high risk for other autosomal aneuploidies, and 66 (24.81%) were at a high risk for chromosomal microdeletions or microduplications. 217 women had accepted invasive prenatal diagnosis and respectively 50, 13, 1, 25, 1 and 18 were confirmed with T21, T18, T13, sex chromosome aneuploidies, autosomal aneuploidies and microdeletions/microduplications, and the positive predictive values were 75.76%, 68.42%, 11.11%, 40.32%, 10% and 35.29%, respectively. For 13 042 women (85.59%), the outcome of pregnancy were successfully followed up. During the follow-up, one false negative case of T21 was discovered. No false positive cases for T13 and T18 were found.@*CONCLUSION@#NIPT has a sound performance for screening T13, T18 and T21, and is also valuable for screening other autosomal aneuploidies, sex chromosome aneuploidies and chromosomal microdeletions/microduplications.

The value of combined CNV-Seq and chromosomal karyotyping for the detection of amniocytic mosaicisms and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of combined copy number variation sequencing (CNV-seq) and chromosomal karyotyping for the diagnosis of amniocytic mosaicisms, in addition with a literature review.@*METHODS@#Forty cases of amniocytic mosaicisms detected at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2021, in addition with 245 mosaicisms retrieved from 11 recent literature were evaluated in terms of detection rate, consistency rate, and pregnancy outcomes.@*RESULTS@#The detection rate of amniocytic mosaicisms was 0.46% (40/8 621) in our center. And its consistency rate with chromosomal karyotyping was 75.0% (30/40). After genetic counseling, 30 (75.0%) couples had opted to terminate the pregnancy, 5 (12.5%) had decided to continue with the pregnancy, 3 (7.5%) fetuses were born alive, and 2 cases (5.0%) were lost in touch. By contrast, 245 cases (0.39%) of mosaicisms were identified among 63 577 amniotic samples, with a consistency rate of 62.8% (103/164) with other techniques. Among these, 114 cases (55.1%) were terminated, 75 (36.2%) were born alive, and 18 (8.7%) were lost during the follow up.@*CONCLUSION@#Combined CNV-seq and chromosomal karyotyping has a high value for the detection of amniotic mosaicisms.

The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses.@*METHODS@#46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis.@*RESULTS@#Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77).@*CONCLUSION@#NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

Clinical and genetic analysis of a fetus with 17q12 microdeletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome.@*METHODS@#A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated.@*RESULTS@#Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome.@*CONCLUSION@#The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.

Genetic analysis of two children with developmental delay and intellectual disability / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of two patients with developmental delay and intellectual disability.@*METHODS@#Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions.@*RESULTS@#Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents.@*CONCLUSION@#The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.

Genetic analysis of a case with mosaicism of a small supernumerary marker chromosome derived from idic(15) / 中华医学遗传学杂志

OBJECTIVE@#To determine the origin of a mosaicism small supernumerary marker chromosome (sSMC) by cytogenetic and molecular analysis.@*METHODS@#Karyotype analysis, fluorescence in situ hybridization (FISH) and SNP-array were carried out.@*RESULTS@#The karyotype of the patient was mos47,XX,+mar[45]/48,XX,+2mar[3]/46,XX[52]; the SNP-array result was arr[hg19]15q11.1q11.2 (20 161 372-24 314 675)×3, and the repeat fragment was about 4.15 Mb. FISH showed that approximately 50% of the cells have contained a sSMC with double D15Z1 probe site segments derived from abnormal idic(15). This sSMC did not contain SNRPN and PML probe fragments of Prader-Willi syndrome/Angelman syndrome.@*CONCLUSION@#When the patient's karyotype and phenotype are inconsistent, cytogenetic and molecular biology technologies should be combined to clarify the karyotype and gene location, so as to provide more accurate genetic consultation for the follow-up treatments.

Genetic testing and analysis of 2 cases of trisomy 11 mosaicism / 南方医科大学学报

Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management.

Application of CNV-seq and chromosomal karyotyping in the prenatal diagnosis for carriers of balanced translocations / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) and karyotyping in the prenatal diagnosis for carriers of balanced translocations.@*METHODS@#Clinical records of 135 amniocentesis samples of balanced translocation carriers undergoing simultaneous CNV-seq and karyotyping were analyzed. Chromosomal aberrations were defined as those can definitely lead to birth defects definitely, which included chromosomal numerical abnormality, large deletion/duplication and pathogenic copy number variations (pCNVs).@*RESULTS@#The detection rates for karyotyping and CNV-seq were 4.44% (6/135) and 5.93% (8/135) respectively, and the latter had a detection rate of 1.48(2/135) higher than the former. A total of 68 fetal chromosomal translocations were detected by karyotying analysis.@*CONCLUSION@#For couples carrying a balanced translocation, simultaneous CNV-seq and karyotyping is conducive to the detection of fetal chromosomal abnormalities and genetic counseling.

A rare case of dicentric ring chromosome and derivative ring chromosome Chimera / 中华医学遗传学杂志

OBJECTIVE@#Utilize high-resolution chromosome analysis and microarray detection to determine the genetic etiology of infertility of a 32-year old female patient.@*METHODS@#The peripheral blood of the patient was cultured for high-resolution chromosome G and C banding karyotype analysis, and then 750K SNP-Array chip detection was performed.@*RESULTS@#Karyotype analysis results showed that the patient's karyotype was 45,XX,-13 [7]/46,XX,r(13) (p13q34) [185]/46,XX,dic r(13;13)(p13q34;p13q34) [14]/ 47,XX,+der(13;13;13;13) (p13q34;p13q34;p13q34; p13q34), dic r(13;13) [1]/ 46,XX [3]. The microarray results showed that the patient had a 3.3 Mb deletion in the 13q34 segment of chromosome 13, which may be related to infertility.@*CONCLUSION@#Infertility of the patient reported in this article may be related to the deletion of chromosome segment (13q34-qter).

Reporte de malformaciones fetales diagnosticadas en comité ecográfico del Hospital Regional de Talca, entre junio 2020 y junio 2021 / Report of fetal malformations diagnosed in the ultrasound committee of the regional hospital of Talca, between june 2020 and june 2021

Introduction: Obstetric ultrasound is part of the screening to select the population at high risk of having a congenital malformation. Considering that fetal defects occur in approximately 2-4 out of every 100 live newborns, and are the cause of 35-40% of perinatal mortality in Chile, it is therefore justified to perform the second trimester ultrasound, which presents a high index prenatal screening (56%), with few false positives. Methods: A retrospective, cross-sectional and descriptive study was carried out, by reviewing 6,385 ultrasound scans, which were performed during one year (June 2020-June 2021), at the Regional Hospital of Talca, where 126 fetuses with suspected malformation were detected. Results: Of the total number of patients evaluated, a congenital malformation rate of 1.9% was detected, with cardiac malformations the most frequent, and diabetes mellitus the main risk factor. Conclusions: Antenatal ultrasound study is essential in the first and second trimesters of pregnancy, followed by a referral to an ultrasound committee, emphasizing early and interdisciplinary management. The frequencies found are similar to those reported in the international bibliography

Uleritema ofriógenes como entidad asociada al síndrome 18p- en un paciente pediátrico / Ulerythema ophryogenes as an entity associated with 18p- syndrome in a pediatric patient

El uleritema ofriógenes es un trastorno cutáneo benigno y poco frecuente que se presenta habitualmente en la infancia. Se caracteriza por pápulas foliculares eritematosas y queratósicas en el lateral de las cejas, que con el tiempo suelen evolucionar a alopecia cicatricial. Dicha entidad puede aparecer como manifestación clínica aislada o asociada a varios síndromes congénitos (18p-, Cornelia de Lange, Noonan y Rubinstein- Taybi, entre otros). Presentamos el caso de un paciente de 13 años con síndrome 18p- que consultó por lesiones puntiformes rugosas al tacto y pérdida de pelo en ambas cejas (uleritema ofriógenes), así como por hiperqueratosis pilar en brazos. Esta tríada, conocida como síndrome de Zouboulis, ha sido poco descrita en la literatura. Se considera que el reconocimiento del uleritema ofriógenes es de crucial importancia ya que, ante su presencia, debería realizarse una anamnesis y una exploración física exhaustivas en búsqueda de otras alteraciones que pudieran orientar a la existencia de un trastorno genético subyacente.

Ulerythema ophryogenes is a benign and rare skin disorder commonly presenting in childhood. It is characterized by erythematous and keratotic follicular papules located on the side of the eyebrows, and which over time tends to evolve into scarred alopecia. This entity may appear as an isolated clinical manifestation or associated with several congenital syndromes (18p-, Cornelia de Lange, Noonan, Rubinstein-Taybi, among others). We present a 13-year-old male with 18p- syndrome who consults for rough lesions and hair loss in both eyebrows (ulerythema ophryogenes), as well as for hyperkeatosis pilaris in both arms. This triad, known as Zouboulis syndrome, has been rarely reported in the literature. We consider that the recognition of ulerythema ophryogenes is of crucial importance since, in view of its presence, comprehensive anamnesis and physical examination should be performed in search of other alterations that could guide the existence of an underlying genetic disord

Síndrome de Rubinstein ­ Taybi: características fenotípicas, reporte de caso / Rubinstein - Taybi syndrome: phenotypic characteristics, case report / Síndrome de Rubinstein - Taybi: características fenotípicas, relato de caso

Introducción: El síndrome de Rubinstein ­ Taybi es una patología de origen genético que afecta a 1 de cada 100.000 a 125.000 nacidos vivos, se caracteriza por presentar: retraso en el crecimiento, retraso en el desarrollo psicomotriz y anomalías morfológicas que incluyen: rasgos faciales peculiares (cejas arqueadas y gruesas, fisuras palpebrales inclinadas hacia abajo, puente nasal convexo con punta de la nariz por debajo de las alas), pulgares y hallux anchos. Su origen epigenético en el 60% de los casos se debe a una alteración en el gen CREBBP (codificador de la proteína CPB), en el 10% a un cambio en el gen EP300 (codificador de la proteína p300) y en el 30% no se han logrado identificar su causa. Caso clínico: Niño de 8 años de edad con retardo en el desarrollo psicomotriz, con dificultades para la adaptación escolar. Al examen físico con rasgos faciales: cejas superpobladas y arqueadas, hirsutismo en frente y región de labio superior, fisuras palpebrales inclinadas hacia abajo, hipertelorismo con estrabismo convergente, puente nasal ancho, nariz achatada, la punta se extiende levemente por debajo de las alas nasales. Con hirsutismo en región cervical e interescapular. En las manos se identifica dedos pulgares anchos, en el resto de dedos se evidencian falanges distales ensanchadas, de igual forma en la región de los pies se identifican hallux anchos y falanges distales ensanchadas. Evolución: El paciente sigue en observación por consulta externa, fue enviado a programas de terapia de lenguaje, lectura y psicomotriz. No ha desarrollado infecciones pulmonares hasta el cierre del seguimiento, 6 meses posteriores al diagnóstico. Conclusión: En presente caso reporta las alteraciones fenotípicas características faciales y de extremidades de un niño con síndrome de Rubinstein-Taybi, las cuales ayudaron al diagnóstico clínico.

Introduction: Rubinstein-Taybi syndrome is a pathology of genetic origin that affects 1 out of every 100,000 to 125,000 live births, it is characterized by: growth retardation, delay in psy-chomotor development and morphological abnormalities that include: peculiar facial features (thick arched eyebrows, downward sloping palpebral fissures, convex nasal bridge with tip of nose below wings), broad thumbs and hallux. Its epigenetic origin in 60% of cases is due to an alteration in the CREBBP gene (coding for CPB protein), in 10% to a change in the EP300 gene (coding for p300 protein) and in the 30% have not been able to identify its cause. Clinical case: 8-year-old boy with a delay in psychomotor development, with difficulties in adapting to school. On physical examination with facial features: overpopulated and arched eyebrows, hirsutism in the forehead and upper lip region, downward sloping palpebral fissures, hypertelorism with convergent strabismus, wide nasal bridge, flattened nose, the tip extends slightly below the nasal wings. With hirsutism in the cervical and interscapular region. In the hands, broad thumbs are identified, in the rest of the fingers there are widened distal phalanges, in the same way in the region of the feet, wide hallux and widened distal phalanges are identified. Evolution: The patient continues to be observed by outpatient consultation, he was sent to speech, reading and psychomotor therapy programs. He has not developed pulmonary infections until the close of follow-up, 6 months after diagnosis. Conclusion: In this case, it reports the phenotypic alterations of the facial and limb characteristics of a child with Rubinstein-Taybi syndrome, which helped the clinical diagnosis.

Introdução: A síndrome de Rubinstein-Taybi é uma patologia de origem genética que afeta 1 em cada 100.000 a 125.000 nascidos vivos, é caracterizada por: retardo de crescimento, atraso no desenvolvimento psicomotor e anormalidades morfológicas que incluem: características faciais peculiares (sobrancelhas arqueadas e grossas, descendente fissuras palpebrais, ponte nasal convexa com a ponta do nariz abaixo das asas), polegares largos e hálux. Sua origem epigenética em 60% dos casos deve-se a uma alteração no gene CREBBP (que codifica a proteína CPB), em 10% a uma alteração no gene EP300 (que codifica a proteína p300) e em 30% sua causa não foi identificada . Caso clínico: Menino de 8 anos com atraso no desenvolvimento psicomotor, com dificuldade de adaptação à escola. No exame físico com características faciais: sobrancelhas superpovoadas e arqueadas, hirsutismo na testa e região do lábio superior, fissuras palpebrais inclinadas para baixo, hipertelorismo com estrabismo convergente, ponte nasal larga, nariz achatado, a ponta se estende ligeiramente abaixo das asas nasais. Com hirsutismo na região cervical e interescapular. Nas mãos identificam-se os polegares largos, nos restantes dedos são identificadas falanges distais alargadas, da mesma forma que na região dos pés, hálux largo e falanges distais alargadas. Evolução: O paciente ainda está em acompanhamento ambulatorial, foi encaminhado para programas de fonoaudiologia. Ele não desenvolveu infecções pulmonares até o fechamento do acompanhamento, 6 meses após o diagnóstico. Conclusão: Nesse caso, relata as alterações fenotípicas das características faciais e de membros de uma criança com síndrome de Rubinstein-Taybi, o que auxiliou no diagnóstico clínico.

Advance of research on Phelan-McDermid syndrome / 中华医学遗传学杂志

Phelan-McDermid syndrome (PMS)(OMIM#606232) is a rare genetic disorder caused by a deletion of the distal long arm of chromosome 22q13 involving a variety of clinical features with considerably heterogeneous degrees of severity. This syndrome is characterized by global developmental delay, intellectual disability, hypotonia, absent or severely delayed speech, minor dysmorphic features and autism spectrum disorder. PMS is easy to be misdiagnosed due to the lack of specific clinical manifestations. SHANK3 has been identified as the critical candidate gene for the neurological features of this syndrome. However, some studies have shown that other genes located in the 22q13 region may have a role in the formation of symptoms in individuals with PMS. This article provides a review for recent progress made in research on PMS including etiology, clinical manifestation, diagnosis, and treatment, with a particular emphasis on clinical diagnosis and treatment.