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2.
Article in Chinese | WPRIM | ID: wpr-879623

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a pedigree affected with hereditary multiple osteochondroma (HMO).@*METHODS@#Peripheral blood samples were collected from the proband and members of his pedigree with informed consent. Following extraction of genomic DNA, all coding exons and flanking intronic sequences (-10 bp) of the EXT1 and EXT2 genes were subjected to targeted capture and next generation sequencing (NGS). Suspected variant was verified by Sanger sequencing.@*RESULTS@#A heterozygous nonsense variant (c.1911C>A) was found in exon 10 of the EXT1 gene in the proband and his affected father but not in a healthy sister and normal controls. The variant was classified as a pathogenic based on the guidelines of the American College of Medical Genetics and Genomics (PVS1+PM2+PP1). Bioinformatic analysis predicted that the c.1911C>A variant may be disease-causing via nonsense-mediated mRNA decay and anomalous splicing.@*CONCLUSION@#The c.1911C>A variant probably underlay the disease in this pedigree. Discovery of this variant enriched the variant spectrum of HMO.


Subject(s)
Codon, Nonsense , Exons/genetics , Exostoses, Multiple Hereditary/genetics , Heterozygote , Humans , Pedigree
3.
Article in Chinese | WPRIM | ID: wpr-879622

ABSTRACT

OBJECTIVE@#To explore the genetic basis of a pedigree affected with Alagille syndrome (ALGS).@*METHODS@#Targeted capture and next generation sequencing was carried out for the proband. Candidate variants were verified by Sanger sequencing among his family members. Their pathogenicity of the variant was predicted with bioinformatic analysis. Clinical characteristics and genotype-phenotype correlation were analyzed.@*RESULTS@#The proband, his elder sister and mother were found to carry a heterozygous c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene, which may lead to premature termination of translation and a truncated protein with loss of function. The variant was unreported previously. The phenotypes of the proband (cholestasis, pulmonary artery stenosis and peculiar faces) have differed from those of his elder sister (cholestasis with pruritus, posterior embryonic ring of cornea) and mother (with no clinical manifestation). Cholestasis and peculiar face of the proband became insignificant with age.@*CONCLUSION@#The c.1270dupG (p.Ala424Glyfs*5) variant of the JAG1 gene probably underlay the ALGS in this pedigree with incomplete penetrance.


Subject(s)
Aged , Alagille Syndrome/genetics , Heterozygote , High-Throughput Nucleotide Sequencing , Humans , Pedigree , Phenotype
4.
Article in Chinese | WPRIM | ID: wpr-879617

ABSTRACT

OBJECTIVE@#To detect gene inversion in two pedigrees affected with Hemophilia A by using Nanopore sequencing technology.@*METHODS@#Peripheral blood samples were taken from members of the two pedigrees. Following extraction of genome DNA, genetic variants of the carriers were detected by Nanopore sequencing and subjected to bioinformatic analysis.@*RESULTS@#Nanopore sequencing has identified the niece of the proband of the pedigree 1 as carrier of Hemophilia A Inv22, and the mother of the proband of the pedigree 2 as carrier of Hemophilia A Inv1, which was consistent with clinical findings. Breakpoint sites in both pedigrees were accurately mapped. Statistical analysis of the sequencing results revealed a large number of variations in the carriers' genomes including deletions, duplications, insertions, inversions and translocations.@*CONCLUSION@#Nanopore sequencing can be used to analyze gene inversions associated with Hemophilia A, which also provided a powerful tool for the diagnosis of diseases caused by gene inversions.


Subject(s)
Chromosome Inversion/genetics , Hemophilia A/genetics , Humans , Introns , Nanopore Sequencing , Pedigree
5.
Article in Chinese | WPRIM | ID: wpr-879612

ABSTRACT

OBJECTIVE@#To delineate the serological and molecular profiles of a patient with A(w)37B subtype.@*METHODS@#The ABO bloodtypes of the proband, his wife and daughter were determined with a standard serological method. Their ABO genotypes were determined by sequence-specific primer polymerase chain reaction (PCR-SSP). All exons of the ABO gene were directly sequenced. Exons 6 and 7 of the ABO gene were further analyzed by cloning and sequencing.@*RESULTS@#The red blood cells of the proband showed a weak B phenotype. His serum sample contained weak reactive anti-A antibody, which was defined as A(w)B blood group based on the serological characteristics. The A and B alleles were detected by blood group genotyping. Gene cloning and sequencing have identified a characteristic c.940A>G variant (ABO*AW.37) in exon 7 of the ABO gene, which resulted in substitution of Lysine by Glutamate at position 314. The proband's daughter has inherited the ABO*AW.37 allele.@*CONCLUSION@#The c.940A>G variant in exon 7 of the ABO gene probably underlay the decreased activity of GTA transferase and resulted in the Aw37 phenotype.


Subject(s)
ABO Blood-Group System/genetics , Alleles , Genotype , Humans , Pedigree , Phenotype
6.
Article in Chinese | WPRIM | ID: wpr-879610

ABSTRACT

OBJECTIVE@#To explore the correlation between DSG2, TTN and GATA4 genes and Brugada syndrome in Henan Province of China.@*METHODS@#From February 2017 to February 2019, 100 patients with Brugada syndrome and 100 healthy individuals were selected as the study and the control groups, respectively. Electrocardiogram and echocardiography were carried out, and peripheral blood samples was collected. Coding regions of DSG2, TTN and GATA4 genes were amplified by PCR and sequenced. The results were compared with standard sequences from GenBank.@*RESULTS@#Electrocardiogram showed that all patients from the study group had ventricular arrhythmia, 87 cases (87%) presented ventricular tachycardia (VT), 84 cases (84%) presented T wave inversion, and 51 cases (51%) presented Epsilon wave. Echocardiography showed that the right ventricle in the study group was enlarged with the inner diameter of the right ventricle being (40.0±13.3) mm, and the right ventricle showed various degree of abnormal systolic function. The enlargement of right atrium accounted for 64%, and the involvement of the left ventricle accounted for 27%. The right ventricular diameter and left ventricular diastolic diameter of the study group were significantly greater than those of the control group (P< 0.05). DNA sequencing showed that 60 patients carried DSG2 gene variants, among which 18 had missense variant of exon 8. Fifty patients carried TTN gene variants, including 8 in the A-band domain and 3 in the I-band domain. Twenty patients carried 3 variants of the GATA4 gene.@*CONCLUSION@#Variants of the DSG2, TTN and GATA4 genes in Henan region are correlated with the onset of Brugada syndrome.


Subject(s)
Arrhythmogenic Right Ventricular Dysplasia , Brugada Syndrome/genetics , China , Connectin , Desmoglein 2/genetics , GATA4 Transcription Factor , Humans , Pedigree , Sequence Analysis, DNA
7.
Article in Chinese | WPRIM | ID: wpr-879606

ABSTRACT

OBJECTIVE@#To explore the genetic variation of a Chinese family affected with congenital insensitivity to pain with anhidrosis and albinism.@*METHODS@#Whole exome sequencing (WES) was carried out to screen potential variants within genomic DNA extracted from the proband and his parents. Whole genome sequencing (WGS) was applied when variants were not found completely. Suspected variants were validated by Sanger sequencing.@*RESULTS@#WES has identified a heterozygous c.1729G>C (p.G577R) variant of NTRK1 gene and two heterozygous variants of OCA2 gene, namely c.1363A>G (p.R455G) and c.1182+1G>A. WGS has identified two additional heterozygous variants c.(851-798C>T; 851-794C>G) in deep intronic regions of the NTRK1 gene.@*CONCLUSION@#The compound heterozygous variants of the NTRK1 gene probably underlay the congenital insensitivity to pain with anhidrosis. And the compound heterozygous variants of the OCA2 gene probably underlay the albinism in the proband. In the case where no variant is detected by WES in the coding region, WGS should be considered to screen potential variants in the whole genome.


Subject(s)
Albinism , Child , DNA Mutational Analysis , Hereditary Sensory and Autonomic Neuropathies/genetics , Heterozygote , Humans , Membrane Transport Proteins , Mutation , Pedigree
8.
Article in Chinese | WPRIM | ID: wpr-879605

ABSTRACT

OBJECTIVE@#To explore the clinical and genetic characteristics of a child with X-linked hypohidrotic ectodermal dysplasia (XLHED).@*METHODS@#Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents with informed consent and subjected to copy number variation (CNV) analysis and whole exome sequencing (WES).@*RESULTS@#The male infant manifested sparse hair, anhidrosis, anuresis due to polycystic kidney dysplasia, external genital malformation and anal atresia. WES has revealed a 406 bp hemizygous deletion at Xq13 (68 836 147-68 836 553) in the proband, which encompassed exon 1 of the EDA gene. A heterozygous deletion at the same site was detected in the mother, while no deletion or duplication of the site was detected in the father.@*CONCLUSION@#The hemizygous deletion of EDA gene exon 1 probably underlay the ectodermal dysplasia in the proband. Above result has provided a basis for genetic counseling and prenatal diagnosis for the family.


Subject(s)
Child , DNA Copy Number Variations , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia 1, Anhidrotic/genetics , Ectodysplasins/genetics , Genetic Testing , Humans , Infant , Male , Pedigree
9.
Article in Chinese | WPRIM | ID: wpr-879603

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome.@*METHODS@#Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Pathological changes of renal basement membrane and expression of COL4A5 protein were analyzed by renal biopsy and immunofluorescence assay, respectively.@*RESULTS@#All patients from the pedigree manifested progressive renal damage, gross hematuria, proteinuria and nephrotic syndrome. Renal biopsy of the proband revealed thickening of the basement membrane. No expression of the COL4A5 gene was detected by immunofluorescence. High-throughput sequencing and Sanger sequencing indicated that the proband has carried a c.3706delC (p.1236Pfs*69) variant in exon 41 of the COL4A5 gene. The same variant was also found in his mother and two brothers whom were similarly affected.@*CONCLUSION@#The novel c.3706delC (p.1236Pfs*69) variant of the COL4A5 gene probably underlay the pathogenesis of X-linked hereditary Alport syndrome in this pedigree. Above findings have enriched the spectrum of COL4A5 gene variants and provided a basis for the diagnosis and genetic counseling for the pedigree.


Subject(s)
Collagen Type IV/genetics , Hematuria , High-Throughput Nucleotide Sequencing , Humans , Male , Mutation , Nephritis, Hereditary/genetics , Pedigree
10.
Article in Chinese | WPRIM | ID: wpr-879601

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with non-syndromic hearing loss (NSHL).@*METHODS@#Commercialized gene chip was applied to detect common mutations associated with congenital deafness. Whole exome sequencing was carried out for patients for whom gene chip yielded a negative result. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Two patients from the pedigree were discovered to carry compound heterozygous variants of the TRIOBP gene, namely c.3299C>A and c.5185-2A>G. Their parents had normal hearing and were both heterozygous carriers of the above variants. Both variants had co-segregated with the disease phenotype in the pedigree and were unreported previously.@*CONCLUSION@#Pathogenic variants of the TRIOBP gene comprise an important factor for NSHL. The novel c.5185-2A>G and c.3299C>A variants discovered in this study have enriched the mutational spectrum of the TRIOBP gene and enabled molecular diagnosis and genetic counseling for the family.


Subject(s)
Deafness/genetics , Hearing Loss, Sensorineural/genetics , Heterozygote , Humans , Microfilament Proteins/genetics , Mutation , Pedigree , Whole Exome Sequencing
11.
Article in Chinese | WPRIM | ID: wpr-879599

ABSTRACT

OBJECTIVE@#To explore the genetic basis for two Chinese pedigrees affected with Huntington disease and provide prenatal diagnosis for them.@*METHODS@#Peripheral venous blood samples were collected from the probands. PCR and capillary gel electrophoresis were used to determine the number of CAG repeats in their IT15 gene. Pre-symptomatic testing was offered to their children and relatives, and prenatal diagnosis was provided to three pregnant women from the two pedigrees.@*RESULTS@#The two probands, in addition with three asymptomatic members, were found to have a (CAG)n repeat number greater than 40. Upon prenatal diagnosis, the numbers of CAG repeats in two fetuses from pedigree 1 were determined as (16, 19) and (18, 19), both were within the normal range. A fetus from pedigree 2 was found to have a CAG repeat number of (15, 41), which exceeded the normal range.@*CONCLUSION@#Genetic testing can facilitate the diagnosis of Huntington disease and avoid further birth of affected children.


Subject(s)
Child , Female , Genetic Testing , Humans , Huntington Disease/genetics , Nerve Tissue Proteins/genetics , Pedigree , Pregnancy , Prenatal Diagnosis
12.
Article in Chinese | WPRIM | ID: wpr-879595

ABSTRACT

OBJECTIVE@#To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019.@*METHODS@#Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing.@*RESULTS@#DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy.@*CONCLUSION@#This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.


Subject(s)
China , Dystrophin/genetics , Exons/genetics , Female , Gene Deletion , Genetic Testing , Humans , Muscular Dystrophy, Duchenne/therapy , Mutation , Pedigree , Pregnancy
13.
Article in Chinese | WPRIM | ID: wpr-879587

ABSTRACT

OBJECTIVE@#To analyze the clinical features of a Chinese pedigree affected with tuberculosis sclerosis and explore its molecular pathogenesis.@*METHODS@#Clinical data of the proband and members of his pedigree were collected. Whole exome sequencing was carried out to detect variants of the TSC1 and TSC2 genes. Candidate variants was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The proband and his mother, who also had mild features of tuberous sclerosis, were found to harbor a novel heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene, which was absent in the 4 healthy relatives. Bioinformatic analysis suggested the variant to be likely pathogenic.@*CONCLUSION@#The heterozygous c.4183C>T (p.Q1395X) variant of the TSC2 gene probably underlay the disease in this pedigree. Above finding has expanded the spectrum of TSC2 gene variants. The more severe symptoms in the proband may be attributed to phenotypic heterogeneity of this disease.


Subject(s)
China , Humans , Mutation , Pedigree , Tuberous Sclerosis/genetics , Tuberous Sclerosis Complex 2 Protein/genetics
14.
Article in Chinese | WPRIM | ID: wpr-879566

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a child with mental and motor retardation, language impairment, facial dysmorphism and epilepsy.@*METHODS@#Whole exome sequencing was carried out to detect pathogenic variant in the proband, and candidate variant was selected based on his phenotype. Sanger sequencing was used to verify the variant in the proband, his parents and other family members.@*RESULTS@#The proband was found to carry a frameshifting mutation of MBD5 gene, namely c.2217delT (p.F739Lfs*6), which was inherited from his mother and unreported previously. Sanger sequencing confirmed that his brother carried the same mutation with a similar phenotype. His mother also had poor language expression when she was young, in addition with poor academic performance, though she could do some housework and had no history of convulsion.@*CONCLUSION@#A novel pathogenic variant of the MBD5 gene was discovered, which has enriched the mutational spectrum of the MBD5 gene. Above discovery has enabled genetic counseling and prenatal diagnosis for the family.


Subject(s)
Child , DNA-Binding Proteins/genetics , Female , Humans , Intellectual Disability/genetics , Male , Mutation , Pedigree , Phenotype , Pregnancy , Whole Exome Sequencing
15.
Article in Chinese | WPRIM | ID: wpr-879564

ABSTRACT

OBJECTIVE@#To detect pathogenic variants in a pedigree affected with propionic acidemia (PA).@*METHODS@#The proband was subjected to high-throughput next-generation sequencing. Suspected variants were validated by Sanger sequencing of his family members. mRNA was extracted from peripheral blood lymphocytes from the proband's father in order to verify the impact of the splicing variant by RT-PCR combined with Sanger sequencing. The pathogenicity of the missense variant was predicted by using PolyPhen-2, Mutation Taster, SIFT, COBALT and HOPE software.@*RESULTS@#The proband was found to harbor compound heterozygous variants of the PCCB gene, namely c.184-2A>G and c.733G>A (p.G245S), which were respectively inherited from his father and mother. RT-PCR combined with Sanger sequencing confirmed skipping of exon 2 during transcription. Bioinformatic analysis indicated the c.733G>A (p.G245S) variant to be damaging.@*CONCLUSION@#The two variants of the PCCB gene probably underlay the disease in this patient. Above findings have enriched the spectrum of PCCB gene variants.


Subject(s)
Exons , Humans , Mutation , Mutation, Missense , Pedigree , Propionic Acidemia/genetics
16.
Article in Chinese | WPRIM | ID: wpr-879563

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing.@*METHODS@#Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing.@*RESULTS@#Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis.@*CONCLUSION@#Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.


Subject(s)
Child , China , DNA Copy Number Variations , Electron Transport , Humans , Mutation , NADH Dehydrogenase/genetics , Pedigree
17.
Article in Chinese | WPRIM | ID: wpr-879562

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a Chinese pedigree affected with coagulation factor XI (FXI) deficiency.@*METHODS@#Activated partial thromboplastin time (APTT) and other blood coagulation factors, and activities of FXI:C and other relevant coagulation factors for a large Chinese pedigree including 6 patients from 3 generations were determined on a Stago automatic coagulometer. The FXI:Ag was determined with an ELISA method. All exons and flanking regions of the F11 gene were subjected to Sanger sequencing. ClustalX-2.1-win software was used to analyze the conservation of amino acids. Pathogenicity of the variants was predicted with online bioinformatics software including Mutation Taster and Swiss-Pdb Viewer.@*RESULTS@#The APTT of the proband was prolonged to 94.2 s. The FXI:C and FXI:Ag were decreased to 1% and 1.3%, respectively. The APTT of her father, mother, son and daughter was 42.1 s, 43.0 s, 42.5 s and 41.0 s, respectively. The FXI:C and FXI:Ag of them were almost halved compared with the normal values. The APTT, FXI:C and FXI:Ag of her husband were all normal. Genetic testing revealed that the proband has carried a heterozygous missense c.1103G>A (p.Gly350Glu) variant in exon 10 and a heterozygous missense c.1556G>A (p.Trp501stop) variant in exon 13 of the F11 gene. The father and daughter were heterozygous for the c.1103G>A variant, whilst the mother and son were heterozygous for the c.1556G>A variant. Both Gly350 and Trp501 are highly conserved among homologous species, and both variants were predicted to be "disease causing" by Mutation Taster. Protein modeling indicated there are two hydrogen bonds between Gly350 and Phe312 in the wild-type, while the p.Gly350Glu variant may add a hydrogen bond to Glu and Tyr351 and create steric resistance between the two, both may affect the structure and stability of protein.@*CONCLUSION@#The c.1103G>A and c.1556G>A compound heterozygous variants probably underlay the pathogenesis of congenital FXI deficiency in this pedigree.


Subject(s)
Exons/genetics , Factor XI/genetics , Factor XI Deficiency/genetics , Female , Heterozygote , Humans , Male , Mutation , Pedigree
18.
Article in Chinese | WPRIM | ID: wpr-879560

ABSTRACT

OBJECTIVE@#To explore the clinical characteristics and genetic basis for a pair of twins affected with hyaline fibromatosis syndrome (HFS).@*METHODS@#Clinical data of the twins were retrospectively analyzed. High-throughput sequencing was carried out to detect potential pathogenic variants. CLUSTALX was employed to analyze cross-species conservation of the mutant amino acids. Impact of the mutations was predicted by using software including PolyPhen-2 and Mutation taster.@*RESULTS@#The pair of twins have featured growth and intelligence retardation, and were found to carry compound heterozygous variants of the ANTXR2 gene including c.1214G>A and c.1074delT, among which c.1214G>A was unreported previously. Both variants were predicted to be pathogenic. In addition to growth and mental delay, the pair of twins also featured hyperplasia of the gum and soft tissue-like masses of the auricle. The younger brother had rupture of the auricle mass during follow-up.@*CONCLUSION@#The patients' condition can probably be attributed to the compound heterozygous variants of the ANTXR2 gene. Above finding has facilitated molecular diagnosis of the patients.


Subject(s)
Asian Continental Ancestry Group/genetics , China , Humans , Hyalinosis, Systemic/genetics , Male , Mutation , Pedigree , Receptors, Peptide/genetics , Retrospective Studies
19.
Article in Chinese | WPRIM | ID: wpr-879554

ABSTRACT

OBJECTIVE@#To analyze the clinical phenotype and genetic variants in five Chinese pedigrees affected with Dysferlinopathy.@*METHODS@#Next generation sequencing (NGS) was carried out for the probands from the five pedigrees. Suspected variants were validated by Sanger sequencing. Pathogenicity of the variants was assessed based on the standards and guidelines by the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#Ten DYSF gene variants (including 5 frameshift variants, 3 splicing variants, 1 missense variant and 1 nonsense variant) were detected. Among these, c.1375dupA (p.Met459Asnfs*15), c.610C>T (p.Arg204X), c.1180+5G>A and c.1284+2T>C were known to be pathogenic, while c.4008_4010delCCTinsAC (p.Leu1337Argfs*8), c.1137_1169del (p.379_390del), c.754A>G(p.Thr252Ala), c.1175_1176insGCAGAGTG (p.Met394Serfs*7), c.3114_3115insCGGC (p.Arg1040Profs*74) and c.1053+3G>C were unreported previously. Of the six novel variants, c.1137_1169del, c.1175_1176insGCAGAGTG and c.3114_3115insCGGC were predicted as pathogenic (PVS1+PM2+PM3), c.4008_4010delCCTinsAC as likely pathogenic (PVS1+PM2), c.754A>G and c.1053+3G>C as variants of uncertain significance based on the ACMG standards and guidelines.@*CONCLUSION@#Variants of the DYSF gene probably underlay Dysferlinopathy in the patients among the five pedigrees. Above finding has enriched the spectrum of DYSF gene variants.


Subject(s)
Humans , Muscular Dystrophies, Limb-Girdle/genetics , Mutation , Pedigree , Phenotype , RNA Splicing
20.
Article in Chinese | WPRIM | ID: wpr-879551

ABSTRACT

OBJECTIVE@#To explore the genetic basis of a pedigree affected with peroneal muscular atrophy.@*METHODS@#Neuroelectrophysiological examination and whole exome sequencing were carried out for the proband, a six-year-and-ten-month-old boy. Suspected variant was verified in his family members through Sanger sequencing. Bioinformatic analysis was carried to predict the conservation of amino acid sequence and impact of the variant on the protein structure and function.@*RESULTS@#Electrophysiological examination showed demyelination and axonal changes of motor and sensory nerve fibers. A heterozygous missense c.1066A>G (p. Thr356Ala) variant was found in exon 11 of the MFN2 gene in the proband and his mother, but not in his sister and father. Bioinformatic analysis using PolyPhen-2 and Mutation Taster software predicted the variant to be pathogenic, and that the sequence of variation site was highly conserved among various species. Based no the American College of Medical Genetics and Genomics standards and guidelines, the c.1066A>G (p. Thr356Ala) variant of MFN2 gene was predicted to be likely pathogenic (PS1+ PM2+ PP3+ PP4).@*CONCLUSION@#The heterozygous missense c.1066A>G (p.Thr356Ala) variant of the MFN2 gene probably underlay the disease in the proband, and the results have enabled genetic counseling and prenatal diagnosis for this family.


Subject(s)
Charcot-Marie-Tooth Disease/genetics , Child , China , Drosophila Proteins/genetics , Exons , Female , Heterozygote , Humans , Male , Membrane Proteins/genetics , Mutation , Pedigree , Pregnancy , Whole Exome Sequencing
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