Aug 2026· Journal of clinical laboratory analysis (Print)· 0 citations· 41 references
Medicine
TL;DR
A novel likely pathogenic variant in the LOXHD1 gene, c.3713dupA (p.Asp1238Glufs*10), was identified and enhances the comprehension of the genetic underpinnings of hearing loss and may aid in molecular diagnostics and genetic counseling for impacted families.
Abstract
ABSTRACT Background Hearing loss is one of the most common sensory disorders caused by genetic and environmental factors. Autosomal recessive non‐syndromic hearing loss (ARNSHL) is extremely heterogeneous, with over 100 genes known to be involved. Hearing loss can result from mutations in the LOXHD1 gene, which codes a highly conserved protein known as lipoxygenase and is located at 18q21.1. Despite the association between LOXHD1 mutations and ARNSHL, there are still few documented cases. Methods We examined a case of non‐syndromic hearing loss in an Iranian family with a history of consanguinity and several affected siblings. Next‐generation sequencing (NGS) was conducted on the proband to discover causal genetic alterations. Sanger sequencing was employed to confirm the identified variation. Results A novel likely pathogenic variant in the LOXHD1 gene, c.3713dupA (p.Asp1238Glufs*10), was identified. Sanger sequencing was used to confirm that the affected family members had this frameshift mutation. Conclusion Our findings broaden the mutational range of LOXHD1 linked to ARNSHL. This unique variant enhances the comprehension of the genetic underpinnings of hearing loss and may aid in molecular diagnostics and genetic counseling for impacted families.
A novel pathogenic variant in the ACTG1 gene responsible for NSHL is identified, which expands the mutational spectrum of ACTG1‐related hearing loss and provides intervention targets for gene therapy of HHL.
Ya-Jing Zhu, Tianyu Wang, Xiang-Lan Sun et al.· Journal of Neural Transplant...· 0 citations
Purpose Hereditary hearing loss is a genetically heterogeneous disorder, with more than 120 genes implicated in the non-syndromic forms. The genetic cause of non-syndromic hearing loss (NSHL) in a Chinese Han family was investigated, and the function of the identified mutation was characterized. Methods The family members were clinically evaluated. Targeted next-generation sequencing of 414 deafness-related genes was performed on the proband. The identified variants were validated in the family members of the proband using Sanger sequencing and PCR. The functional impacts of the variants on splicing were predicted using SpliceAI and MaxEntScan. Results Two compound heterozygous CDH23 mutations (c.7054+1G>A and c.4209+794_4825 del) were identified in a thirteen-month-old girl with NSHL. Sanger sequencing confirmed recessive inheritance, with each unaffected parent carrying a single heterozygous variant. The c.7054+1G>A variant is a canonical splice donor variant predicted to severely disrupt splicing (SpliceAI donor loss score: 0.99; MaxEntScan score reduced from 10.28 in the wild-type to 2.10 in the mutant, a 79.57% reduction). The c.4209+794_4825 del is a 6.45 kb heterozygous deletion encompassing exons 35–38, predicted to resulted in the in-frame skipping of exons 35–38. AlphaFold-based structural modeling revealed marked conformational changes in the mutant extracellular domain, supporting the hypothesis that these variants compromised CDH23-mediated tip-link formation and mechanotransduction. Conclusion We identified two novel compound heterozygous CDH23 mutations (c.7054+1G>A and c.4209+794_4825 del) in a Chinese Han family, expanding the known spectrum of CDH23 mutation and adding to the understanding of the genotype–phenotype correlations in NSHL.
Pengcheng Xu, Qi Liao, Yun Lin et al.· International Journal of Gen...· 0 citations
The predicted loss-of-function of SLITRK6 supports an important role for SLITRK6 in auditory and visual system development and is consistent with previously described SLITRK6-associated HL with myopia.
The particular phenotype that was observed in the patient is comparable to the ones that are described in the KCTD7 related pathologies, combined with segregation analysis indicating both parents carried the variant heterogeneously present is a strong indication that the identified mutation consists of probably pathogenic mutation.
S. Alharazy, Peter Natesan Pushparaj, Rose Jelani et al.· Pakistan Journal of Medical...· 0 citations
The co-occurrence of variants in AKAP4 and RNF220 may suggest an oligogenic etiology of NOA and contribute to the phenotypic variability associated with AKAP4 variants.
Razieh Ebrahimi Askari, A. Malcher, Fateme Sefid et al.· International Journal of Mol...· 0 citations
It is demonstrated that even in the absence of functional experiments, comprehensive family analysis can provide crucial clues for variant of uncertain significance (VUS) interpretation.
Xiulan Hao, Yanchou Ye, Man Liu et al.· Frontiers in Genetics· 0 citations
