International journal of pediatric otorhinolaryngology · 2023
Novel WFS1 mutations in patients with low-to-middle frequency hearing loss.
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Guo Luo, Gu Xiaodong, Sun Qin, Zhang Yike, Li Huawei, Du Qiang
Аннотация
BACKGROUND: Hearing loss (HL) is the most common sensorineural disorder in human. It is estimated that genetic factors contribute to over 50% of prelingual hearing loss. Most of dominant HHL patients manifest postlingual progressive hearing loss that mainly affect high frequencies. However, mutations in a few dominant HL genes, such as WFS1, TECTA and DIAPH1, cause distinct audiogram that primarily affects the low and middle frequencies.
METHODS: We recruited twelve independent HL families with worse low or middle frequency audiograms. Each proband of these families was excluded for pathogenic mutations in GJB2, SLC26A4, and MT-RNR1 genes. Mutation screening was performed by whole exome sequencing. Next, candidate variants were validated in each family by sanger sequencing.
RESULTS: Six heterozygous WFS1 variants were identified in six families, including three novel mutations (c.2519T > G, p.F840C; c.2048T > G, p.M683R and c.2419A > C, p.S807R) and three previously reported variants (c.2005T > C, p.Y669H; c.2590G > A, p.E864K and c.G2389A, p.D797 N). All the novel mutations were absent in 100 ethnically matched controls and were predicted to be deleterious by multiple algorithms.
CONCLUSIONS: We identified three novel and three previously reported WFS1 mutations in six unrelated Chinese families. Our findings enriched the genotype-phenotype spectrum of WFS1 related NSHL. Additional genotype-phenotype correlation study will clarify the detailed phenotypic range caused by WFS1 mutations.
METHODS: We recruited twelve independent HL families with worse low or middle frequency audiograms. Each proband of these families was excluded for pathogenic mutations in GJB2, SLC26A4, and MT-RNR1 genes. Mutation screening was performed by whole exome sequencing. Next, candidate variants were validated in each family by sanger sequencing.
RESULTS: Six heterozygous WFS1 variants were identified in six families, including three novel mutations (c.2519T > G, p.F840C; c.2048T > G, p.M683R and c.2419A > C, p.S807R) and three previously reported variants (c.2005T > C, p.Y669H; c.2590G > A, p.E864K and c.G2389A, p.D797 N). All the novel mutations were absent in 100 ethnically matched controls and were predicted to be deleterious by multiple algorithms.
CONCLUSIONS: We identified three novel and three previously reported WFS1 mutations in six unrelated Chinese families. Our findings enriched the genotype-phenotype spectrum of WFS1 related NSHL. Additional genotype-phenotype correlation study will clarify the detailed phenotypic range caused by WFS1 mutations.