Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss

Hong, Xia; Huang, Xiangjun; Guo, Yi; Hu, Pengzhi; He, Guangxiang; Deng, Xiong; Xu, Hongbo; Yang, Zhijian; Deng, Hao

doi:10.1371/journal.pone.0136306

Cited by 30 publications

(18 citation statements)

References 53 publications

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“…Additionally, two newly identified mutations (e.g., p.Q3172X/p.V2632L ) of MYO15A were noticed in the J07 family, and the subjects presented severe hearing loss. These results were in line with the fact that MYO15A mutation may be associated with severe or extremely severe hearing loss among subjects [ 13 , 14 ].…”

Section: Discussionsupporting

confidence: 79%

Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique

Chen

Kuyaxi

et al. 2018

Disease Markers

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We aim to identify the mutations of deafness genes using massively parallel DNA sequencing in the 12 Uyghur families. SNPscan method was used to screen against the 124 sites in the common deafness genes in probands. Subjects with SNPscan negativity were subject to massively parallel DNA sequencing for the sequencing of 97 genes known to be responsible for hearing loss. Eight families (66.7%) showed biallelic mutations in probands, including MYO15A mutation (6892C>T in J02 family, 9514C>T/7894G>T in J07 family, and 9514C>T in J16 family), MYO7A mutation (1258A>T in J03 family), TMC1 mutation (773G>A in J09 family and 1247T>G/1312G>A in J11 family), and PCDH15 mutation (4658delT in J08 and J13 families). Six novel types of mutation were identified including 6892C>T, 9514C>T/7894G>T, and 9514C>T in MYO15A gene, 1258A>T in MYO7A, 773G>A in TMC1, and 4658delT in PCDH15. The ratio of nonsense mutation and frameshift mutation was comparatively high. All these indicated that the mutation types reported in this study were rare. In conclusion, rare deafness genes were identified in the Uyghur families using massively parallel DNA sequencing, part of which were suggested to be related to the pathogenesis of the disease.

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Section: Discussionsupporting

confidence: 79%

Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique

Chen

Kuyaxi

et al. 2018

Disease Markers

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“…[Ammar‐Khodja et al., ], [Atik et al., ], [Bademci et al., ],[Bashir et al., ], [Belguith et al., ], [Brownstein et al., ], [Brownstein et al., ], [Cengiz et al., ], [Chang et al., ], [Chen et al., ], [Diaz‐Horta et al., ], [Duman et al., ], [Fattahi et al., ], [Gao et al., ], [Gu et al., ], [Imtiaz et al., ], [Kalay et al., ], [Lezirovitz et al., ], [Li et al., ], [Liburd et al., ], [Miyagawa et al., ; Miyagawa et al., ], [Miyagawa et al., ], [Moteki et al., ], [Nal et al., ], [Neveling et al., ], [Park et al., ], [Rehman et al., ], [Riahi et al., ], [Schrauwen et al., ], [Shafique et al., ], [Shahin et al., ], [Shearer et al., ], [Sloan‐Heggen et al., ], [Sloan‐Heggen et al., ], [Vona et al., ], [Vozzi et al., ], [Wang et al., ], [Woo et al., ], [Xia et al., ], [Yano et al., ], [Yang et al., ]…”

Section: Articles Cited In the Online Supporting Informationmentioning

confidence: 99%

Mutational Spectrum ofMYO15Aand the Molecular Mechanisms of DFNB3 Human Deafness

et al. 2016

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Deafness in humans is a common neurosensory disorder and is genetically heterogeneous. Across diverse ethnic groups, mutations of MYO15A at the DFNB3 locus appear to be the third or fourth most common cause of autosomal recessive, nonsyndromic deafness. In 49 of the 67 exons of MYO15A, there are currently 192 recessive mutations identified, including 14 novel mutations reported here. These mutations are distributed uniformly across MYO15A with one enigmatic exception; the alternatively spliced giant exon 2, encoding 1,233 residues, has 17 truncating mutations but no convincing deafness-causing missense mutations. MYO15A encodes three distinct isoform classes, one of which is 395 kDa (3,530 residues), the largest member of the myosin superfamily of molecular motors. Studies of Myo15 mouse models that recapitulate DFNB3 revealed two different pathogenic mechanisms of hearing loss. In the inner ear, myosin 15 is necessary both for the development and the long-term maintenance of stereocilia, mechanosensory sound-transducing organelles that extend from the apical surface of hair cells. The goal of this Mutation Update is to provide a comprehensive review of mutations and functions of MYO15A.

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“…Studies have shown that MYO15A plays an important role in the elongation and development of static cilia and actin laments, the cohesiveness of the stereocilia also results from the interaction between the whirlin and MYO15A genes [10]. When a pathogenic mutation occurs in the MYO15A gene, ciliary dyskinesia can cause deafness [11]. Rehman Au et al [12] reported 192 recessive mutations in 49 out of the 67 exons of MYO15A.…”

Section: Discussionmentioning

confidence: 99%

Molecular etiology of hereditary deafness using next generation sequencing in northwest China

Wang¹,

Li²,

Ding³

et al. 2020

Preprint

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Objective: To analyze the molecular etiology of 92 hereditary deafness families and explore the genetic mechanism of newly identified genes in deafness heritability. Methods: We analyzed the medical history, audiology, imaging, and physical examination data of 92 probands and their family members. Probands were selected from the hereditary deafness database; they did not have any of the common genetic mutation sites. Genomic DNA was extracted from blood samples and next generation sequencing was performed on an Illumina platform, followed by co-segregation analysis of family members. The control group included the clinical data and blood samples from 207 normal hearing people. Results: Among the 92 samples, 30 homozygous variants were identified in 29 autosomal recessive hereditary deafness families, including 6 reported mutations and 26 novel mutations. Among them, MYO15A was the most frequently detected (6/92), followed by mutations in CDH23, OTOF, FGF3 (3/92 each), MYO7A, SLC26A4, MYO6 (2/92 each), BSND, CLDN14, DFNB59, ILDR1, LHFPL5, LRTOMT, TMPRSS3, TPRN, USH1C, and LOXHD1 (1/92 each). Conclusion: In patients with autosomal recessive deafness, the MYO15A, CDH23, OTOF, and FGF3 genes could be used as candidate genes for conventional genetic studies in northwest China.

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Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss

Cited by 30 publications

References 53 publications

Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique

Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique

Mutational Spectrum ofMYO15Aand the Molecular Mechanisms of DFNB3 Human Deafness

Molecular etiology of hereditary deafness using next generation sequencing in northwest China

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