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. 2022 Oct;36(10):e24653.
doi: 10.1002/jcla.24653. Epub 2022 Aug 10.

Identification of novel compound heterozygous mutations of the MYO15A gene with autosomal recessive non-syndromic hearing loss

Luming Wang  1 , Yue Zhang  1 , Qiuxia Xue  1 , Pinghua Huang  1 , Xiaodan Liu  1
Affiliations

Identification of novel compound heterozygous mutations of the MYO15A gene with autosomal recessive non-syndromic hearing loss

Luming Wang et al. J Clin Lab Anal. 2022 Oct.

Abstract

Background: The most common inheritance pattern responsible for congenital deafness belongs to autosomal recessive non-syndromic hearing loss (ARNSHL) and mutations of the highly heterogeneous MYO15A locus are present in a large proportion of cases.

Methods: One Chinese family with ARNSHL was subjected to clinical evaluation and genetic analysis. We used targeted and whole exome sequencing with Sanger sequencing to identify and characterize mutations. Bioinformatics analysis was conducted to evaluate molecular functions.

Results: Three compound heterozygous MYO15A gene variants, including two novel variants, c.6804G > A (p.M2268I), and c.6188_6190delinsGTCA (p.F2063Cfs*60), responsible for deafness were identified. Pathogenicity was assessed by multiple bioinformatics analyses.

Conclusion: We identified novel mutations of the MYO15A locus associated with ARNSHL in a Chinese family. The current findings expand the MYO15A pathogenic mutation spectrum to assist with genetic counseling and prenatal diagnosis.

Keywords: MYO15A; hearing loss; mutation; targeted exome sequencing; whole exome sequencing.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
Pedigree: Proband is marked by an arrow with P
FIGURE 2
FIGURE 2
ABR testing of the newborn child. The threshold of binaural V‐wave response shows left ear >97 dB nHL (A) and right ear = 97 dB nHL (B)
FIGURE 3
FIGURE 3
Sanger sequencing of the four mutations in five family members
FIGURE 4
FIGURE 4
Multiple species sequence alignment of p.M2268 and p.F2063 variants of MYO15A
FIGURE 5
FIGURE 5
3D simulation modeling of wild‐type and mutated MYO15A protein structure. (A) Simulations of wild‐type and p.M2268I variants. (B) Simulations of wild‐type and p.F2063Cfs*60 variants
FIGURE 6
FIGURE 6
Schematic showing the location of MYO15A mutations. Novel mutations are marked by red boxes
See this image and copyright information in PMC

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