ABSTRACT
This paper examines how participants in genetic counseling sessions interactionally manage situations where the results of tests to investigate the causes of identified fetal malformations are inconclusive or missing. The dataset consists of 54 audio-recorded interactions at a unit specialized in moderate- and high-risk pregnancies at a Brazilian public hospital. Conversation analysis was used to examine the data, revealing that the participants deployed interactional actions that exhibited highly negative valence toward diagnostic inconclusiveness, demonstrating that when there is a motivation for a medical examination, insofar as its results will serve as a basis for subsequent decision-making (in this case about future pregnancies), there is a preference for bad diagnostic news over absent or inconclusive diagnostic news. These findings are consistent with prior interactional studies.
Este artigo examina como os participantes em sessões de aconselhamento genético gerenciam interacionalmente resultados de testes genéticos inconclusivos ou ausentes testes para investigar as causas das malformações fetais identificadas. O conjunto de dados consiste em 54 interações gravadas em áudio em uma unidade de gestação de médio e alto risco de um hospital público brasileiro. A abordagem da Análise da Conversa utilizada para examinar os dados revela que os participantes desenvolvem ações interacionais que exibem uma orientação de valência altamente negativa em relação à inconclusividade diagnóstica, demonstrando que quando há motivação para um exame médico, ou seja, usando o resultado do teste diagnóstico como base para tomada de decisão, tal como acontece com futuras gestações, haja uma preferência por más notícias diagnósticas em detrimento de notícias diagnósticas ausentes ou inconclusivas. Tais resultados são consistentes com estudos interacionais anteriores.
Este artículo examina cómo los participantes en las sesiones de asesoramiento genético gestionan de forma interactiva los resultados de pruebas genéticas no concluyentes o faltantes, pruebas para investigar las causas de las malformaciones fetales identificadas. El conjunto de datos consta de 54 interacciones grabadas en audio en una unidad de embarazo de riesgo medio y alto de un hospital público brasileño. El enfoque de Análisis de Conversación utilizado para examinar los datos revela que los participantes desarrollan acciones interaccionales que exhiben una orientación de valencia altamente negativa hacia la falta de conclusión del diagnóstico, lo que demuestra que cuando hay motivación para un examen médico, es decir, utilizar el diagnóstico del resultado de la prueba como base para la toma de decisiones, como ocurre con futuros embarazos, se prefieran las malas noticias diagnósticas a las noticias diagnósticas ausentes o no concluyentes. Estos resultados son consistentes con estudios interaccionales previos.
Subject(s)
Congenital Abnormalities , Genetic Testing , Decision Making , Observational Study , Genetic Counseling , Medical Examination , Diagnostic Techniques and Procedures , Counseling , MethodsABSTRACT
La clorhidrorrea congénita es un trastorno genético infrecuente pero importante caracterizado por una alteración grave del balance hidroelectrolítico como resultado de un defecto en la absorción intestinal de cloruros. Los niños afectados presentan diarrea persistente, deshidratación y malnutrición; el control médico y del desarrollo son complejos. Mejorar la detección prenatal es esencial para facilitar la atención del paciente, las intervenciones tempranas y el asesoramiento genético informado. Sin embargo, a pesar de los avances de la medicina, la naturaleza compleja y la escasa frecuencia de esta entidad, constituyen un desafío para la detección prenatal. En este estudio, se reporta el caso de una embarazada donde los estudios por imágenes de resonancia magnética fetales identificaron en forma efectiva las características típicas de la clorhidrorrea congénita. Se proveen conocimientos sobre las complejidades del diagnóstico y se sugieren caminos para las estrategias de detección temprana de esta enfermedad.
Congenital chloride diarrhea (CCD) is a rare but significant genetic disorder characterized by severe electrolyte imbalances resulting from impaired intestinal chloride absorption. Affected children experience persistent diarrhea, dehydration, and malnutrition, complicating medical and developmental care. The enhancement of prenatal detection is crucial for improved patient management, early interventions, and informed genetic counseling. However, despite advancements in medicine, the complex nature and rarity of CCD make prenatal detection challenging. In this study, we report a fetal case where prenatal magnetic resonance imaging (MRI) effectively identified the distinctive characteristics of CCD, providing insights into the complexities of diagnosis and suggesting avenues for enhanced early detection strategies.
Subject(s)
Humans , Female , Pregnancy , Prenatal Diagnosis/methods , Diarrhea/congenital , Metabolism, Inborn Errors/diagnosis , Metabolism, Inborn Errors/genetics , Diarrhea/etiology , Genetic CounselingABSTRACT
OBJECTIVE@#To explore the genetic basis for a pregnant woman with a history of adverse pregnancy outcomes.@*METHODS@#A woman with an adverse history of pregnancies including one fetal demise and two induced abortions due to fetal diaphragmatic hernia and complex cardiac anomalies was selected as the study subject. Muscle tissue from the induced abortus was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the couple and other family members.@*RESULTS@#Genetic sequencing revealed that the fetus has harbored a frameshift variant of the KDM6A gene (NM_001291415.2), namely c.1228_1229del (p.Gln410GlufsTer2), which was inherited from the woman and her mother. The variant was unreported previously, and the woman was found to have short stature, sparse eyebrows in the outer third, peculiar facial features, but normal intelligence in addition with female congenital genital malformation, like incomplete vaginal septum, double cervix, double uterus, and unilateral ovary absence. mostly similar phenotypes observed in her mother.@*CONCLUSION@#The hemizygous c.1228_1229del variant of the KDM6A gene probably underlay the abnormalities in the fetus. All findings have enabled genetic counseling for this family featuring X-linked inheritance, and the woman had given birth to a healthy girl with appropriate prevention and intervention.
Subject(s)
Female , Humans , Pregnancy , China , Fetus , Genetic Counseling , Histone Demethylases/genetics , Mutation , PedigreeABSTRACT
OBJECTIVE@#To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).@*METHODS@#A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.
Subject(s)
Child , Pregnancy , Humans , Female , Fetus , Genetic Counseling , Genomics , Kidney , Mutation , PhenotypeABSTRACT
Genetic counseling for hearing loss today originated from decoding the genetic code of hereditary hearing loss, which serves as an effective strategy for preventing hearing loss and constitutes a crucial component of the diagnostic and therapeutic framework. This paper described the main principles and contents of genetic counseling for hearing loss, the key points of counseling across various genetic models and its application in tertiary prevention strategies targeting hearing impairment. The prospects of an AI-assisted genetic counseling decision system and the envisions of genetic counseling in preventing hereditary hearing loss were introduced. Genetic counseling for hearing loss today embodies the hallmark of a new era, which is inseparable from the advancements in science and technology, and will undoubtedly contribute to precise gene intervention!
Subject(s)
Humans , Genetic Counseling , Deafness/genetics , Hearing Loss/diagnosis , Hearing Loss, Sensorineural/geneticsABSTRACT
Hereditary endocrine and metabolic diseases , caused by genetic factors, exhibit complex and diverse symptoms, including the possibility of concurrent sensorineural deafness. Currently, there is a limited clinical understanding of hereditary endocrine and metabolic diseases that manifest with deafness, the pathogenesis remains unclear,and there is a lack of effective diagnostic and treatment methods. This article summarizes the research progress of hereditary endocrine and metabolic diseases complicated with deafness from the pathogenesis, clinical phenotype, diagnosis and treatment. Understanding the current research progress and integrating genetic analysis into clinical practice are crucial for accurate diagnosis and treatment, evaluating clinical efficacy, and providing effective genetic counseling for these diseases.
Subject(s)
Humans , Deafness/genetics , Hearing Loss, Sensorineural/diagnosis , Phenotype , Metabolic Diseases/genetics , Genetic CounselingABSTRACT
Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.
Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.
Subject(s)
Humans , Female , Breast Neoplasms/prevention & control , Risk Factors , Endometrial Neoplasms/prevention & control , Genetic Counseling , Genital Neoplasms, Female/prevention & control , Genetic Diseases, InbornABSTRACT
After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.
Subject(s)
Female , Humans , Pregnancy , Asian People , Chromosome Aberrations , Chromosome Deletion , Chromosome Duplication/genetics , DNA Copy Number Variations/genetics , Fetal Diseases/genetics , Genetic Counseling , Microarray Analysis , Prenatal Care , Prenatal Diagnosis , Practice Guidelines as TopicABSTRACT
Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.
Subject(s)
Humans , Female , Middle Aged , Adult , Genetic Counseling , Genetic Predisposition to Disease , Breast Neoplasms/surgery , Ovarian Neoplasms/surgery , MutationABSTRACT
Objective: To investigate the genetic, clinical and pathological characteristics of families with hereditary breast-ovarian cancer syndrome (HBOCS) and to explore the implementation of genetic counseling and preventive surgery. Methods: Four siblings with HBOCS in Cancer Hospital/Chinese Academy of Medical Sciences were selected as the study subjects. BRCA gene testing and genetic counseling were performed, family history was traced and family map was drawn. Results: There were 7 cancer patients (Ⅰ 2, Ⅱ 4, Ⅱ 8, Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) in three generations in the family. One patient (Ⅲ 7) had breast cancer and ovarian cancer successively. The first generation (Ⅰ 2) developed cancer at age 60, the second generation (Ⅱ4 and Ⅱ8) developed cancer at 55. The third generation (Ⅲ 7, Ⅲ 10, Ⅲ 11, Ⅲ 12) developed cancer at the age of 42-50 years. Four HBOCS patients were treated in our hospital, and all of them were found to have deleterious BRCA1 mutation. Two had already developed ovarian cancer (Ⅲ 10, Ⅲ 12), while in one case (Ⅲ 11), tubal carcinoma was found during preventive total hysterectomy and pelvic lymph node metastasis was found after the supplementary staging surgery. The other patient without cancer underwent preventive bilateral salpingectomy(Ⅲ 15). Conclusion: The HBOCS family reported in this study is relatively rare, the onset time of tumor was younger generation by generation. It is very important to pay attention to the genetic counseling of ovarian cancer patients and to timely detect the HBOCS families for genetic testing and prophylactic surgery.
Subject(s)
Humans , Female , Middle Aged , Adult , Genetic Counseling , Genetic Predisposition to Disease , Breast Neoplasms/surgery , Ovarian Neoplasms/surgery , MutationABSTRACT
OBJECTIVE@#To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM).@*METHODS@#A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients.@*RESULTS@#This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic.@*CONCLUSION@#The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.
Subject(s)
Humans , Computational Biology , Genetic Counseling , Genomics , Mutation , Neurodevelopmental Disorders/genetics , Dyskinesias , GTP-Binding Protein alpha Subunits, Gi-GoABSTRACT
OBJECTIVE@#To analyze the clinical data and genetic characteristics of a child with fibrocartilage hyperplasia type 1 (FBCG1).@*METHODS@#A child who was admitted to Gansu Provincial Maternity and Child Health Care Hospital on January 21, 2021 due to severe pneumonia and suspected congenital genetic metabolic disorder was selected as the study subject. Clinical data of the child was collected, and genomic DNA was extracted from peripheral blood samples from the child and her parents. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing.@*RESULTS@#The patient, a 1-month-old girl, had presented with facial dysmorphism, abnormal skeletal development, and clubbing of upper and lower limbs. WES revealed that she has harbored compound heterozygous variants c.3358G>A/c.2295+1G>A of the COL11A1 gene, which has been associated with fibrochondrogenesis. Sanger sequencing has verified that the variants have been respectively inherited from her father and mother, both of whom were phenotypically normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.3358G>A variant was graded as likely pathogenic (PM1+PM2_Supporting+PM3+PP3), and so was the c.2295+1G>A variant (PVS1＋PM2_Supporting).@*CONCLUSION@#The compound heterozygous variants c.3358G>A/c.2295+1G>A probably underlay the disease in this child. Above finding has facilitated definite diagnosis, genetic counseling for her family.
Subject(s)
Female , Humans , Infant , Abnormalities, Multiple , Collagen Type XI/genetics , Genetic Counseling , Genomics , MutationABSTRACT
OBJECTIVE@#To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity.@*METHODS@#A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic.@*CONCLUSION@#The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.
Subject(s)
Female , Humans , Child, Preschool , Computational Biology , East Asian People , Genetic Counseling , Genomics , Mutation , Obesity, Morbid/genetics , Pediatric Obesity/geneticsABSTRACT
OBJECTIVE@#To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS).@*METHODS@#A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents. Trio-Whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the POMT2 gene, namely c.471delC (p.F158Lfs*42) and c.1975C>T (p.R659W), which were respectively inherited from its father and mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively rated as pathogenic (PVS1+PM2_Supporting+PP4) and likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).@*CONCLUSION@#Trio-WES may be used for the prenatal diagnosis of WWS. The compound heterozygous variants of the POMT2 gene probably underlay the disorder in this fetus. Above finding has expanded the mutational spectrum of the POMT2 gene and enabled definite diagnosis and genetic counseling for the family.
Subject(s)
Pregnancy , Child , Female , Humans , Walker-Warburg Syndrome , Prenatal Diagnosis , Fetus , Genetic Counseling , Genomics , MutationABSTRACT
OBJECTIVE@#To explore the clinical and genetic characteristics of a fetus with Melnick-Needles syndrome (MNS).@*METHODS@#A fetus with MNS diagnosed at Ningbo Women and Children's Hospital in November 2020 was selected as the study subject. Clinical data was collected. Pathogenic variant was screened by using trio-whole exome sequencing (trio-WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#Prenatal ultrasonography of the fetus had shown multiple anomalies including intrauterine growth retardation, bilateral femur curvature, omphalocele, single umbilical artery, and oligohydramnios. Trio-WES revealed that the fetus has harbored hemizygous c.3562G>A (p.A1188T) missense variant of the FLNA gene. Sanger sequencing confirmed that the variant was maternally derived, whilst its father was of a wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The hemizygous c.3562G>A (p.A1188T) variant of the FLNA gene probably underlay the structural abnormalities in this fetus. Genetic testing can facilitate accurate diagnosis of MNS and provide a basis for genetic counseling for this family.
Subject(s)
Child , Female , Humans , Pregnancy , Abnormalities, Multiple/genetics , Fetal Growth Retardation , Fetus , Filamins/genetics , Genetic Counseling , Mutation , OsteochondrodysplasiasABSTRACT
OBJECTIVE@#To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD).@*METHODS@#A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children's Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant.@*CONCLUSION@#The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
Subject(s)
Humans , Male , Child, Preschool , Computational Biology , DNA-Binding Proteins , Genetic Counseling , Genomics , Heart Defects, Congenital/genetics , Mutation , Parents , RNA-Binding Proteins , Developmental Disabilities/geneticsABSTRACT
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/geneticsABSTRACT
OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with recurrent fetal hydrocephalus.@*METHODS@#A couple who had presented at the Affiliated Hospital of Putian College on March 3, 2021 was selected as the study subject. Following elective abortion, fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple, and were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the B3GALNT2 gene, namely c.261-2A>G and c.536T>C (p.Leu179Pro), which were inherited from its father and mother, respectively.According to the guidelines of American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM2_Supporting; PM3+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants of the B3GALNT2 gene probably underlay the α-dystroglycanopathy in this fetus. Above results have provided a basis for genetic counseling of this pedigree.