Novel Compound Heterozygous TMC1 Mutations Associated with Autosomal Recessive Hearing Loss in a Chinese Family

Abstract Background Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation A Chinese family with two offspring–patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.

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Compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia

Medicine ◽

10.1097/md.0000000000012870 ◽

2018 ◽

Vol 97 (44) ◽

pp. e12870 ◽

Cited By ~ 1

Author(s):

Bangzhe Feng ◽

Guangfei Sun ◽

Qingxia Kong ◽

Qiubo Li

Keyword(s):

Autosomal Recessive ◽

Chinese Family ◽

Compound Heterozygous ◽

Compound Heterozygous Mutations

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Autosomal Recessive Congenital Sensorineural Hearing Loss due to a Novel Compound Heterozygous PTPRQ Mutation in a Chinese Family

Neural Plasticity ◽

10.1155/2018/9425725 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Xia Wu ◽

Shan Wang ◽

Sen Chen ◽

Ying-ying Wen ◽

Bo Liu ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Tyrosine Phosphatase ◽

Sensorineural Hearing ◽

Paternal Allele ◽

Chinese Family ◽

Compound Heterozygous ◽

Gene Encoding ◽

Sequencing Method ◽

And Function

PTPRQ gene, encoding protein tyrosine phosphatase receptor Q, is essential for the normal maturation and function of hair bundle in the cochlea. Its mutations can cause the defects of stereocilia in hair cell, which lead to nonsyndromic sensorineural hearing loss. Using next-generation sequencing and Sanger sequencing method, we identified a novel compound heterozygous missense mutation, c.4472C>T p.T1491M (maternal allele) and c.1973T>C p.V658A (paternal allele), in PTPRQ gene. The two mutations are the first reported to be the cause of recessively inherited sensorineural hearing loss. Hearing loss levels and progression involved by PTPRQ mutations among the existing cases seem to be varied, and the relationship between genotypes and phenotypes is unclear. Our data here further prove the important role of PTPRQ in auditory function and provide more information for the further mechanism research of PTPRQ-related hearing loss.

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Compound heterozygous POMT1 mutations in a Chinese family with autosomal recessive muscular dystrophy-dystroglycanopathy C1

Journal of Cellular and Molecular Medicine ◽

10.1111/jcmm.13068 ◽

2017 ◽

Vol 21 (7) ◽

pp. 1388-1393 ◽

Cited By ~ 13

Author(s):

Pengzhi Hu ◽

Song Wu ◽

Lamei Yuan ◽

Qiongfen Lin ◽

Wen Zheng ◽

...

Keyword(s):

Muscular Dystrophy ◽

Autosomal Recessive ◽

Chinese Family ◽

Compound Heterozygous

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Identification of Novel TMC1 Compound Heterozygous Mutations Related to Autosomal Recessive Hearing Loss by Targeted Capture Sequencing

Scientific Journal of Genetics and Gene Therapy ◽

10.17352/sjggt.000009 ◽

2016 ◽

Vol 2 (1) ◽

pp. 013-016

Author(s):

Gao Xue ◽

Huang Sha-Sha ◽

Su Yu ◽

Xu Jin-Cao ◽

Dai Pu

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Compound Heterozygous ◽

Targeted Capture ◽

Compound Heterozygous Mutations ◽

Capture Sequencing

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Audiological features in Serbian patients with hearing impairment identified with c.35delG in the GJB2 gene

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh201117098d ◽

2021 ◽

pp. 98-98

Author(s):

Bojana Dobric ◽

Danijela Radivojevic ◽

Jovana Jecmenica ◽

Vassos Neocleous ◽

Pavlos Fanis ◽

...

Keyword(s):

Hearing Loss ◽

Hearing Impairment ◽

Autosomal Recessive ◽

Gjb2 Gene ◽

Compound Heterozygous ◽

Heterozygous State ◽

Phenotype Correlation ◽

Pathogenic Variants ◽

Environmental Causes ◽

35Delg Mutation

Introduction/Objective. Hearing impairment (HI) is the most common sensorineural disorder with an incidence of 1/700-1000 newborns. Variants in the GJB2 gene are the major cause of autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). The degree of HI in patients with detected mutations in GJB2 gene ranges from mild to profound. The aim of this study was to determine possible genotype-phenotype association between audiometric characteristics and detected genotypes in ARNSHL patients from Serbia. Methods. Ninety-two patients with ARNSHL underwent genetic analysis with PCR-ARMS and sequencing of the GJB2 gene. Audiological analyses were obtained in all patients using a combination of several methods to estimate the degree of hearing loss. Results. Audiological analysis performed in the 92 probands showed moderate to profound range of hearing loss. All identified pathogenic variants accounted for 42.39% of the mutant alleles (78/184 alleles), with the c.35delG mutation being the most frequent (30.43%). Genotype-phenotype correlation in an isolated group of 37 patients bearing c.35delG in the homozygous, compound heterozygous or heterozygous state. In this group the majority of patients (30/37, 81.08%) exhibited severe to profound hearing deficit. Conclusion. Association between genotype and the degree of hearing impairment in patients analyzed in this study demonstrated that patients with bi-allelic truncating mutations i.e. c.35delG, associate with the more severe hearing loss when compared with those identified with only one affected allele. The various degrees of hearing impairment observed in heterozygous patients could be explained by the presence of an undetected second mutation or other modifier genes or environmental causes.

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Identification of Novel Compound Heterozygous MYO15A Mutations in Two Chinese Families with Autosomal Recessive Nonsyndromic Hearing Loss

Neural Plasticity ◽

10.1155/2021/9957712 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Xiao-Hui Wang ◽

Le Xie ◽

Sen Chen ◽

Kai Xu ◽

Xue Bai ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Bioinformatics Analysis ◽

Compound Heterozygous ◽

Congenital Deafness ◽

Chinese Families ◽

Novel Variants ◽

Common Causes ◽

Compound Heterozygous Variants ◽

Generation Sequencing

Congenital deafness is one of the most common causes of disability in humans, and more than half of cases are caused by genetic factors. Mutations of the MYO15A gene are the third most common cause of hereditary hearing loss. Using next-generation sequencing combined with auditory tests, two novel compound heterozygous variants c.2802_2812del/c.5681T>C and c.5681T>C/c.6340G>A in the MYO15A gene were identified in probands from two irrelevant Chinese families. Auditory phenotypes of the probands are consistent with the previously reported for recessive variants in the MYO15A gene. The two novel variants, c.2802_2812del and c.5681T>C, were identified as deleterious mutations by bioinformatics analysis. Our findings extend the MYO15A gene mutation spectrum and provide more information for rapid and precise molecular diagnosis of congenital deafness.

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