A novel nonsense mutation in MYO15A is associated with non-syndromic hearing loss: a case report

Ma, Di; Shen, Songdong; Gao, Hui; Guo, Hui; Lin, Yan‐Hui; Hu, Yuhua; RuanZhang, Zhang; Wang, Sha-yan

doi:10.1186/s12881-018-0657-y

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…Coincidentally, two families (family 1,607,486 and 707,757) in our study shared one identical novel variant, c.7396-1G > A. The remaining 12 variants were previously reported: p.Pro286Serfs*15 [12], p.Ser1176Valfs*14 [13], p.Gly1418Arg [14], p.Ser1481Pro [15–17], c.4596 + 1G > A [18], c.5964 + 3G > A [19, 20], p.Arg1993Trp [21], p.Val2266Met [22], p.Arg2775His, p.Trp2931Glyfs*103, p.Phe3420del [20, 21, 23] and p.Ser3474Gly [24]. Co-segregation of these variations with ARNSHL in the families was confirmed using Sanger sequencing.…”

Section: Resultsmentioning

confidence: 99%

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

et al. 2019

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Background MYO15A variants are responsible for human non-syndromic autosomal recessive deafness ( DFNB3 ). The majority of MYO15A variants are associated with a congenital severe-to-profound hearing loss phenotype, except for MYO15A variants in exon 2, which cause a milder auditory phenotype, suggesting a genotype-phenotype correlation of MYO15A . However, MYO15A variants not in exon 2 related to a milder phenotype have also been reported, indicating that the genotype-phenotype correlation of MYO15A is complicated. This study aimed to provide more cases of MYO15A variation with diverse phenotypes to analyse this complex correlation. Methods Fifteen Chinese autosomal recessive non-syndromic hearing loss (ARNSHL) individuals with MYO15A variants (8 males and 7 females) from 14 unrelated families, identified by targeted gene capture of 127 known candidate deafness genes, were recruited. Additionally, we conducted a review of the literature to further analyses all reported MYO15A genotype-phenotype relationships worldwide. Results We identified 16 novel variants and 12 reported pathogenic MYO15A variants in 15 patients, two of which presented with a milder phenotype. Interestingly, one of these cases carried two reported pathogenic variants in exon 2, while the other carried two novel variants not in exon 2. Based on our literature review, MYO15A genotype-phenotype correlation analysis showed that almost all domains were reported to be correlated with a milder phenotype. However, variants in the N-terminal domain were more likely to cause a milder phenotype. Using next-generation sequencing (NGS), we also found that the number of known MYO15A variants with milder phenotypes in Southeast Asia has increased in recent years. Conclusion Our work extended the MYO15A variant spectrum, enriched our knowledge of auditory phenotypes, and tried to explore the genotype-phenotype correlation in different populations in order to investigate the cause of the complex MYO15A genotype-phenotype correlation. Electronic supplementary material The online version of this article (10.1186/s12881-019-0790-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

et al. 2019

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“…Among these, autosomal recessive non-syndromic hearing loss (ARNSHL) is the prevailing hereditary pattern [ 3 ]. Currently, there have been reports of 105 genetic loci and 67 genes associated with hereditary deafness in ARNSHL (Hereditary Hearing Loss Homepage, http://hereditaryhearingloss.org ), and the genes GJB2, SLC26A4, MYO15A, OTOF, and CDH23 are frequently implicated in ARNSHL [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Novel compound heterozygous MYO15A splicing variants in autosomal recessive non-syndromic hearing loss

Zheng,

Lin,

Gao

et al. 2024

BMC Med Genomics

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Background Hereditary hearing loss is a highly heterogeneous disorder. This study aimed to identify the genetic cause of a Chinese family with autosomal recessive non-syndromic sensorineural hearing loss (ARNSHL). Methods Clinical information and peripheral blood samples were collected from the proband and its parents. Two-step high-throughput next-generation sequencing on the Ion Torrent platform was applied to detect variants as follows. First, long-range PCR was performed to amplify all the regions of the GJB2, GJB3, SLC26A4, and MT-RNR1 genes, followed by next-generation sequencing. If no candidate pathogenetic variants were found, the targeted exon sequencing with AmpliSeq technology was employed to examine another 64 deafness-associated genes. Sanger sequencing was used to identify variants and the lineage co-segregation. The splicing of the MYO15A gene was assessed by in silico bioinformatics prediction and minigene assays. Results Two candidate MYO15A gene (OMIM, #602,666) heterozygous splicing variants, NG_011634.2 (NM_016239.3): c.6177 + 1G > T and c.9690 + 1G > A, were identified in the proband, and these two variants were both annotated as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Further bioinformatic analysis predicted that the c.6177 + 1G > T variant might cause exon skipping and that the c.9690 + 1G > A variant might activate a cryptic splicing donor site in the downstream intronic region. An in vitro minigene assay confirmed the above predictions. Conclusions We identified a compound heterozygous splicing variant in the MYO15A gene in a Han Chinese family with ARNSHL. Our results broaden the spectrum of MYO15A variants, potentially benefiting the early diagnosis, prevention, and treatment of the disease.

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“…Among these, autosomal recessive nonsyndromic hearing loss (ARNSHL) is the prevailing hereditary pattern [3]. Currently, there have been reports of 105 genetic loci and 67 genes associated with hereditary deafness in ARNSHL (Hereditary Hearing Loss Homepage, http://hereditaryhearingloss.org), and the genes GJB2, SLC26A4, MYO15A, OTOF, and CDH23 are frequently implicated in ARNSHL [4].…”

Section: Introductionmentioning

confidence: 99%

Novel Compound Heterozygous MYO15A Splicing Variants in Autosomal Recessive Non-syndromic Hearing Loss

Zheng,

Lin,

Gao

et al. 2023

Preprint

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Background:Hereditary hearing loss is ahighly heterogeneous disorder both genetically and clinically. In this study, we aimed to identify the genetic cause of a Chinese family with autosomal recessive nonsyndromic sensorineural hearing loss (ARNSHL). Methods:Clinical information and peripheral blood samples were collected from the proband and its parents. Two-stephigh-throughput next-generation sequencing on theIon Torrent platform was applied to detect mutations as follows. First, long-range PCR was performed to amplify the entire regions of the GJB2, GJB3, SLC26A4 and MT-RNR1 genes, and the products were submitted to next-generation sequencing. Targeted exon sequencing with AmpliSeq technology was further performed to examine another 64 deafness-associated genes. The identified variants and the cosegregationwith disease phenotypes in the family were validated by Sanger sequencing. We then assessed the effect of the mutation on the splicing of the MYO15A gene by bioinformatics prediction and minigene assays. Results:Two candidate MYO15A gene heterozygous splicing mutations, c.6177+1G>T and c.9690+1G>A, were identified in the proband, and these two variants were both annotated as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Further bioinformatic analysis predicted that thec.6177+1G>T mutation might cause exon skipping and that the c.9690+1G>A mutation might activate a cryptic splicing donor site in the downstream intronic region. An in vitro minigene assay confirmed the above predictions. Conclusions:We identified a compound heterozygous splicing mutation in the MYO15A gene in a Han Chinese family with ARNSHL. Our results broaden the spectrum of MYO15A mutations, potentially benefiting the early diagnosis, prevention and treatment of the disease.

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A novel nonsense mutation in MYO15A is associated with non-syndromic hearing loss: a case report

Cited by 7 publications

References 23 publications

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

Genotype-phenotype correlation analysis of MYO15A variants in autosomal recessive non-syndromic hearing loss

Novel compound heterozygous MYO15A splicing variants in autosomal recessive non-syndromic hearing loss

Novel Compound Heterozygous MYO15A Splicing Variants in Autosomal Recessive Non-syndromic Hearing Loss

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