Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.009
Filter
1.
Rev. Hosp. Ital. B. Aires (2004) ; 43(3): 143-146, sept. 2023. ilus, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1517927

ABSTRACT

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/metabolism
2.
Chinese Journal of Preventive Medicine ; (12): 949-954, 2023.
Article in Chinese | WPRIM | ID: wpr-985501

ABSTRACT

Mosaic embryos contain two or more genetically distinct cell lines, which can be detected by pre-implantation genetic testing for aneuploidy. At present, it has been reported that mosaic embryo transfer can lead to healthy live births. In order to prevent severe adverse pregnancy outcomes, such as implantation failure, abortion, congenital malformation and neonatal death after implantation of mosaic embryos, it is critical to carry out genetic counseling, prenatal diagnosis and pregnancy supervision for mosaic embryo transfer. This article reviews the selection of mosaic embryos, the pregnancy outcomes of mosaic embryo transfer, and the safety of offspring, in order to provide references for the clinical practice of mosaic embryo transfer.


Subject(s)
Pregnancy , Female , Infant, Newborn , Humans , Preimplantation Diagnosis , Embryo Transfer , Pregnancy Outcome , Genetic Testing , Embryo Implantation/genetics
3.
Chinese Medical Journal ; (24): 807-814, 2023.
Article in English | WPRIM | ID: wpr-980820

ABSTRACT

BACKGROUND@#Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).@*METHODS@#We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.@*RESULTS@#We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.@*CONCLUSION@#Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.


Subject(s)
Child , Humans , Neurodevelopmental Disorders/epidemiology , Genetic Testing , Phenotype , Brain/pathology , Genetic Background , SOX Transcription Factors/genetics
4.
Chinese Journal of Medical Genetics ; (6): 847-850, 2023.
Article in Chinese | WPRIM | ID: wpr-981834

ABSTRACT

OBJECTIVE@#To explore the clinical feature and genetic etiology of a patient with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) due to variant of CHD7 gene.@*METHODS@#A patient who had presented at Anhui Provincial Children's Hospital in October 2022 was selected as the study subject. Clinical data of the patient was collected. The patient and his parents were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient had featured delayed development of secondary sexual characteristics but normal olfactory function. Genetic testing revealed that he has harbored a c.3052C>T (p.Pro1018Ser) missense variant of the CHD7 gene, for which both of his parents were of the wild type. The variant has not been recorded in the PubMed and HGMD databases. Analysis of amino acid sequences suggested that the variant site is highly conserved, and the variant may affect the stability of protein structure. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3032C>T variant was classified as a likely pathogenic (PS2+PM2_Supporting+PP2+PP3+PP4).@*CONCLUSION@#The delayed development of secondary sexual characteristics of the patient may be attributed to the c.3052C>T (p.Pro1018Ser) variant of the CHD7 gene. Above finding has expanded the variation spectrum of the CHD7 gene.


Subject(s)
Child , Humans , Male , Amino Acid Sequence , Computational Biology , DNA Helicases/genetics , DNA-Binding Proteins/genetics , Genetic Testing , Genomics , Hypogonadism/genetics , Mutation
5.
Chinese Journal of Medical Genetics ; (6): 842-846, 2023.
Article in Chinese | WPRIM | ID: wpr-981833

ABSTRACT

OBJECTIVE@#To explore the clinical features and genetic basis of a child with Galactosemia.@*METHODS@#A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing.@*RESULTS@#Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR).@*CONCLUSION@#Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.


Subject(s)
Child , Female , Humans , Galactosemias/genetics , Genetic Testing , Health Status , Methionine , Muscle Hypotonia , Mutation
6.
Chinese Journal of Medical Genetics ; (6): 833-837, 2023.
Article in Chinese | WPRIM | ID: wpr-981831

ABSTRACT

OBJECTIVE@#To report on two children with Kabuki syndrome due to variants of the KMT2D gene and summarize their clinical and genetic characteristics.@*METHODS@#Two children who had presented at the Ningbo Women and Children's Hospital respectively on August 19 and November 10, 2021 were selected as the study subjects. Clinical data were collected. Both children were subjected to whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.@*RESULTS@#Both children had featured motor and language developmental delay, facial dysmorphism and mental retardation. Genetic testing revealed that both had harbored de novo heterozygous variants of the KMT2D gene, namely c.10205del (p.Leu3402Argfs*3) and c.5104C>T (p.Arg1702*), both of which were rated as pathogenic variants based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The c.10205del (p.Leu3402Argfs*3) and c.5104C>T (p.Arg1702*) variants of the KMT2D gene probably underlay the pathogenesis in these two children. Above finding has not only provided a basis for their diagnosis and genetic counseling, but also enriched the spectrum of KMT2D gene variants.


Subject(s)
Child , Female , Humans , Abnormalities, Multiple/genetics , Intellectual Disability/genetics , Genetic Counseling , Genetic Testing , Mutation
7.
Chinese Journal of Medical Genetics ; (6): 828-832, 2023.
Article in Chinese | WPRIM | ID: wpr-981830

ABSTRACT

OBJECTIVE@#To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS).@*METHODS@#Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed.@*RESULTS@#Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3;PM2_Supporting).@*CONCLUSION@#Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.


Subject(s)
Child , Humans , Williams Syndrome/diagnosis , Genetic Testing , Facies , Epilepsy/genetics , Chromosomes, Human, Pair 7/genetics , Chromosome Deletion
8.
Chinese Journal of Medical Genetics ; (6): 815-820, 2023.
Article in Chinese | WPRIM | ID: wpr-981828

ABSTRACT

OBJECTIVE@#To analyze the clinical significance of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province.@*METHODS@#Results of audiological examinations, including transient evoked otoacoustic emission and automatic discriminative auditory brainstem evoked potentials, for 6 723 newborns born in Yuncheng area from January 1, 2021 to December 31, 2021, were retrospectively analyzed. Those who failed one of the tests were considered to have failed the examination. A deafness-related gene testing kit was used to detect 15 hot spot variants of common deafness-associated genes in China including GJB2, SLC26A4, GJB3, and mtDNA12S rRNA. Neonates who had passed the audiological examinations and those who had not were compared using a chi-square test.@*RESULTS@#Among the 6 723 neonates, 363 (5.40%) were found to carry variants. These have included 166 cases (2.47%) with GJB2 gene variants, 136 cases (2.03%) with SLC26A4 gene variants, 26 cases (0.39%) with mitochondrial 12S rRNA gene variants, and 33 cases (0.49%) with GJB3 gene variants. Among the 6 723 neonates, 267 had failed initial hearing screening, among which 244 had accepted a re-examination, for which 14 cases (5.73%) had failed again. This has yielded an approximate prevalence of hearing disorder of 0.21% (14/6 723). Among 230 newborns who had passed the re-examination, 10 (4.34%) were found to have carried a variant. By contrast, 4 out of the 14 neonates (28.57%) who had failed the re-examination had carried a variant, and there was a significant difference between the two groups (P < 0.05).@*CONCLUSION@#Genetic screening can provide an effective supplement to newborn hearing screening, and the combined screening can provide a best model for the prevention of hearing loss, which can enable early detection of deafness risks, targeted prevention measures, and genetic counseling to provide accurate prognosis for the newborns.


Subject(s)
Infant, Newborn , Humans , Connexins/genetics , Retrospective Studies , Deafness/genetics , Connexin 26/genetics , Neonatal Screening/methods , Mutation , Genetic Testing/methods , China/epidemiology , Hearing , DNA Mutational Analysis
9.
Chinese Journal of Medical Genetics ; (6): 787-794, 2023.
Article in Chinese | WPRIM | ID: wpr-981824

ABSTRACT

OBJECTIVE@#To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).@*METHODS@#Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES).@*RESULTS@#All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant.@*CONCLUSION@#The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.


Subject(s)
Child , Humans , Acyl-CoA Dehydrogenase/genetics , Carnitine , Genetic Testing , Lipid Metabolism, Inborn Errors/genetics , Neonatal Screening
10.
Chinese Journal of Medical Genetics ; (6): 781-786, 2023.
Article in Chinese | WPRIM | ID: wpr-981823

ABSTRACT

OBJECTIVE@#To explore the genetic basis for four patients suspected for Marfan syndrome (MFS).@*METHODS@#Four male patients with suspected MFS and their family members who were treated at West China Second Hospital of Sichuan University from September 12, 2019 to March 27, 2021 were selected as the study subjects. Peripheral venous blood samples were collected from the patients and their parents or other pedigree members for the extraction of genomic DNA. Whole exome sequencing was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the variants was determined based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#Genetic testing revealed that all four patients have harbored variants of the FBN1 gene, including c.430_433del (p.His144fs) deletional variant in exon 5, c.493C>T (p.Arg165*) nonsense variant in exon 6, c.5304_5306del (p.Asp1768del) deletional variant in exon 44 and c.5165C>G (p.Ser1722Cys) missense variant in exon 42. According to the ACMG guidelines, the c.430_433del and c.493C>T were classified as pathogenic variants (PVS1+PM2_Supporting+PP4; PVS1+PS1+PS2+PM2_Supporting+PP4). c.5304_5306del and c.5165C>G were classified as likely pathogenic variants (PS2+PM2_Supporting+PM4+PP4; PS2_Moderate+PS1+PM1+PM2_Supporting).@*CONCLUSION@#The c.430_433del and c.5304_5306del variants of the FBN1 gene identified in this study were unreported previously. Above results have enriched the variation spectrum of the FBN1 gene and provided a basis for genetic counseling and prenatal diagnosis of patients with MFS and acromicric dysplasia.


Subject(s)
Female , Pregnancy , Humans , Male , Exons , China , Family , Genetic Counseling , Genetic Testing , Marfan Syndrome/genetics , Mutation , Fibrillin-1/genetics
11.
Chinese Journal of Medical Genetics ; (6): 655-660, 2023.
Article in Chinese | WPRIM | ID: wpr-981803

ABSTRACT

OBJECTIVE@#To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations.@*METHODS@#Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA).@*RESULTS@#Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous E7 deletion and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ² = 0.497, P = 0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated.@*CONCLUSION@#This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.


Subject(s)
Humans , Child , Pregnancy , Male , Female , Adult , Homozygote , Sequence Deletion , Prenatal Diagnosis , Genetic Testing , Muscular Atrophy, Spinal/genetics , Survival of Motor Neuron 1 Protein/genetics , Genetic Carrier Screening
12.
Chinese Journal of Medical Genetics ; (6): 641-647, 2023.
Article in Chinese | WPRIM | ID: wpr-981801

ABSTRACT

OBJECTIVE@#To assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases.@*METHODS@#A total of 2 060 neonates born at Ningbo Women and Children's Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA).@*RESULTS@#Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%).@*CONCLUSION@#Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.


Subject(s)
Child , Infant, Newborn , Humans , Female , Prospective Studies , Connexins/genetics , Connexin 26/genetics , Glucosephosphate Dehydrogenase Deficiency , Mutation , Sulfate Transporters/genetics , DNA Mutational Analysis , Genetic Testing/methods , Deafness/genetics , Neonatal Screening/methods , Hearing Loss, Sensorineural/genetics , High-Throughput Nucleotide Sequencing , Solute Carrier Family 22 Member 5/genetics
13.
Chinese Journal of Medical Genetics ; (6): 618-623, 2023.
Article in Chinese | WPRIM | ID: wpr-981800

ABSTRACT

Chromosomal mosaicism (CM) is a common phenomenon in preimplantation genetic testing (PGT). In embryos with CM, genetic contents of trophoblastic ectodermal (TE) cells may be different from that of the inner cell mass (ICM) which will develop into the fetus. Embryos with low mosaic proportion could give rise to healthy live births after transplantation, but are accompanied with high pregnancy risks such as high abortion rate. In order to provide a more comprehensive understanding for CM embryos, this article has systematically summarized the recent progress of research on the definition, mechanism, classification, PGT techniques, self-correction mechanism, transplantation outcome and treatment principles for CM embryos.


Subject(s)
Pregnancy , Female , Humans , Preimplantation Diagnosis/methods , Mosaicism , Aneuploidy , Genetic Testing/methods , Blastocyst
14.
Article in Portuguese | LILACS | ID: biblio-1434511

ABSTRACT

Objetivos: revisar os estudos clínicos acerca de biomarcadores para o câncer cervical publicados nos últimos 10 anos, com foco no diagnóstico, prognóstico e avaliação do tratamento. Metodologia: as bases de dados PubMed, Web of Science e Science Direct foram pesquisadas utilizando os descritores "Uterine Cervical Neoplasms" e "Biomarkers". Foram selecionados os artigos originais publicados em inglês ou português, no período de 2011 a 2021. Após uma triagem pelos títulos e resumos dos artigos, aqueles relacionados ao objetivo do estudo foram lidos integralmente para a decisão final de inclusão na revisão. Os trabalhos que atenderam todos os critérios de seleção tiveram seus dados extraídos, principalmente, no que se refere ao tipo e objetivo do biomarcador proposto, população do estudo, tamanho da amostra, metodologia utilizada e principais desfechos obtidos. Resultados: esta estratégia de busca e seleção resultou em 22 artigos publicados nos últimos 10 anos na temática de interesse. Ocorreu um grande empenho na investigação de biomarcadores séricos para o câncer cervical, com a vantagem de serem minimamente invasivos. Houve destaque para marcadores genéticos e moleculares, como aqueles voltados para a metilação do DNA, detecção de polimorfismos, padrões de expressão de micro-RNA e expressão de genes relacionados à proliferação, imortalização e invasão celular. Conclusão: os dados reunidos encorajam a ampliação das pesquisas para aprimorar e validar a eficiência destes biomarcadores em grandes populações. É evidente o potencial dos biomarcadores como estratégia para melhorar o manejo do diagnóstico e o tratamento do câncer cervical, sendo que a utilização de marcadores genéticos parece ser o futuro dos biomarcadores para o câncer cervical


Aims: to review clinical studies on biomarkers for cervical cancer published in the last 10 years, focusing on the diagnosis, prognosis, and treatment evaluation. Methods: PubMed, Web of Science, and Science Direct databases were searched using the descriptors "Uterine Cervical Neoplasms" and "Biomarkers". Original articles published in English or Portuguese from 2011 to 2021 were selected. After screening by the titles and abstracts of the articles, those related to the objective of the study were read in full for the final decision of inclusion in the review. The studies that met all the selection criteria had their data extracted, especially regarding the type and objective of the biomarker proposed, study population, sample size, methodology used, and main outcomes obtained. Results: this search and selection strategy resulted in 22 articles published in the last 10 years on the topic of interest. There was a great effort to investigate serum biomarkers for cervical cancer, with the advantage of being minimally invasive. There was an emphasis on genetic and molecular markers, such as those focused on DNA methylation, detection of polymorphisms, expression patterns of microRNA, and expression of genes related to cell proliferation, immortalization, and invasion.Conclusions: the data gathered encourage expanded research to improve and validate the efficiency of these biomarkers in large populations. The potential of biomarkers as a strategy to improve the management of cervical cancer diagnosis and treatment is evident, and the use of genetic markers appears to be the future of biomarkers for cervical cancer


Subject(s)
Humans , Female , Biomarkers, Tumor , Uterine Cervical Neoplasms/diagnosis , Prognosis , Uterine Cervical Neoplasms/therapy , Genetic Testing , Early Detection of Cancer , Clinical Decision-Making
15.
Chinese Journal of Contemporary Pediatrics ; (12): 265-271, 2023.
Article in Chinese | WPRIM | ID: wpr-971071

ABSTRACT

OBJECTIVES@#To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis.@*METHODS@#Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed.@*RESULTS@#A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×109/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05).@*CONCLUSIONS@#The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.


Subject(s)
Child , Humans , Male , Female , Child, Preschool , Leukemia, Myelomonocytic, Juvenile/therapy , Prognosis , Genetic Testing , Mutation , Hematopoietic Stem Cell Transplantation
16.
Chinese Journal of Contemporary Pediatrics ; (12): 98-103, 2023.
Article in Chinese | WPRIM | ID: wpr-971046

ABSTRACT

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.


Subject(s)
Adult , Child , Humans , Adrenergic Uptake Inhibitors/therapeutic use , Atomoxetine Hydrochloride/therapeutic use , Attention Deficit Disorder with Hyperactivity/genetics , Cytochrome P-450 CYP2D6/therapeutic use , Drug Monitoring , Genetic Testing , Propylamines/therapeutic use , Treatment Outcome
17.
Chinese Journal of Medical Genetics ; (6): 354-359, 2023.
Article in Chinese | WPRIM | ID: wpr-970932

ABSTRACT

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID).@*METHODS@#The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs.@*RESULTS@#The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+3 weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA.@*CONCLUSION@#The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.


Subject(s)
Female , Humans , Pregnancy , Young Adult , Disks Large Homolog 4 Protein , DNA Copy Number Variations , Fetus , Genetic Testing , Intellectual Disability/genetics , Pregnant Women
18.
Chinese Journal of Medical Genetics ; (6): 349-353, 2023.
Article in Chinese | WPRIM | ID: wpr-970931

ABSTRACT

OBJECTIVE@#To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene.@*METHODS@#Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature.@*RESULTS@#The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed.@*CONCLUSION@#Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.


Subject(s)
Child , Humans , China , Dwarfism , Genetic Testing , Heterozygote , Syndrome
19.
Chinese Journal of Medical Genetics ; (6): 322-327, 2023.
Article in Chinese | WPRIM | ID: wpr-970926

ABSTRACT

OBJECTIVE@#To explore the clinical manifestations and genetic characteristics of patients with congenital central hypothyroidism due to variants of IGSF1 gene.@*METHODS@#Clinical data, results of genetic testing, and follow-up of four patients admitted to Children's Hospital of Soochow University during 2017 to 2021 were retrospectively analyzed.@*RESULTS@#All of the four patients were males. Patient 1 had presented neonatal jaundice, patients 2 and 3 were admitted for growth retardation during childhood, and thyroid function test indicated slightly low free thyroxine (FT4), patient 4 was found to have reduced FT4 in the neonatal period. Genetic testing revealed that all of the four patients have harbored pathogenic variants of the IGSF1 gene, which were all inherited from their mothers. The thyroid functions in all patients were well controlled with oral levothyroxine and regular follow-up.@*CONCLUSION@#Pathogenic variants of the IGSF1 gene probably underlay the congenital central hypothyroidism with a variety of clinical manifestations, and genetic testing can facilitate the diagnosis at an early stage.


Subject(s)
Child , Male , Infant, Newborn , Female , Humans , Retrospective Studies , Hypothyroidism/genetics , Genetic Testing , Mothers , Immunoglobulins/genetics , Membrane Proteins/genetics
20.
Chinese Journal of Medical Genetics ; (6): 295-300, 2023.
Article in Chinese | WPRIM | ID: wpr-970922

ABSTRACT

OBJECTIVE@#To study the molecular epidemiology of thalassemia in Jiaxing area of Zhejiang province and provide a basis for prenatal diagnosis, genetic counseling and prevention and control of birth defects.@*METHODS@#A total of 24 003 pregnant women who presented at the Jiaxing Maternal and Child Health Care Hospital from April 2017 to September 2021 were enrolled. Capillary hemoglobin electrophoresis in combination with routine blood test were used for primary screening for carriers of thalassemia-associated mutations, and those with positive results were subjected to fluorescence quantitative PCR assay. Prenatal diagnosis was provided for couples with a risk of giving birth to children with intermediate or severe thalassemia.@*RESULTS@#Among the 24 003 pregnant women, 1 211 cases were suspected as carriers of thalassemia-associated mutations, among whom 443 (36.58%) were confirmed by genetic testing. Among these, carriers of α-, β- and α-complex β-globin gene mutations have accounted for 27.31% (121/443), 70.65% (313/443) and 2.04% (9/443), respectively. The result of prenatal diagnosis for an at-risk couple was --SEA/αCSα, and the fetus was predicted to have intermediate or severe thalassemia. Termination of the pregnancy was recommended.@*CONCLUSION@#Hemoglobin electrophoresis combined with routine blood test during pregnancy may be used as a preliminary screening measure for carriers of thalassemia-associated variants. Combined with genetic testing, this will be of great significance for the control of thalassemia in this region.


Subject(s)
Female , Humans , Pregnancy , Electrophoresis, Capillary , Genetic Counseling , Genetic Testing , Mutation , Prenatal Diagnosis , Thalassemia/genetics
SELECTION OF CITATIONS
SEARCH DETAIL