Human ; Communication ; Counseling ; Family ; Genetic Counseling ; Risk

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!
Humans ; Genetic Counseling ; Deafness/genetics* ; Hearing Loss/diagnosis* ; Hearing Loss, Sensorineural/genetics*

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.
Humans ; Deafness/genetics* ; Hearing Loss, Sensorineural/diagnosis* ; Phenotype ; Metabolic Diseases/genetics* ; Genetic Counseling

Humans ; Genetic Counseling ; Consensus ; Hypogonadism/genetics*

Child ; Humans ; Genetic Counseling ; Consensus ; Genetic Testing

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.
Humans ; Computational Biology ; Genetic Counseling ; Genomics ; Mutation ; Neurodevelopmental Disorders/genetics* ; Dyskinesias ; GTP-Binding Protein alpha Subunits, Gi-Go

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.
Female ; Humans ; Infant ; Abnormalities, Multiple ; Collagen Type XI/genetics* ; Genetic Counseling ; Genomics ; Mutation

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.
Female ; Humans ; Computational Biology ; East Asian People ; Genetic Counseling ; Genomics ; Mutation ; Obesity, Morbid/genetics* ; Child, Preschool ; Pediatric Obesity/genetics*

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.
Pregnancy ; Child ; Female ; Humans ; Walker-Warburg Syndrome ; Prenatal Diagnosis ; Fetus ; Genetic Counseling ; Genomics ; Mutation

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.
Child ; Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Fetal Growth Retardation ; Fetus ; Filamins/genetics* ; Genetic Counseling ; Mutation ; Osteochondrodysplasias