Salame Malak, Bonnet Crystel, Singh-Estivalet Amrit, Brahim Selma Mohamed, Roux Solene, Boussaty Ely Cheikh, Hadrami Mouna, Hamed Cheikh Tijani, Sidi Abdellahi M'hamed, Veten Fatimetou, Petit Christine, Houmeida Ahmed
Unité de Recherche Sur Les Biomarqueurs Dans La Population Mauritanienne, UN-FST, Nouakchott, Mauritania.
Institut d'Hépato-Virologie, Nouakchott, Mauritania.
J Appl Genet. 2024 Sep 4. doi: 10.1007/s13353-024-00903-x.
PJVK gene was recently shown to create hypervulnerability to sound in humans and was the first human gene implicated in non-syndromic hearing impairment due to neural defect. Targeted next-generation sequencing of over 150 known deafness genes was performed in the proband. Sanger sequencing was used to validate the PJVK variant and confirm familial segregation of the disease. A minigene-based assay has been performed to assess the impact of the variant on splicing. We identified a novel c.550-6A > G acceptor splice-site variant in the PJVK gene in the homozygous state in a Mauritanian child with severe to profound congenital deafness. The substitution was located in intron 4. The effect of the variation was demonstrated by a minigene assay which showed that the variation, an insertion of an additional 5 bp, created a new splice site resulting in the appearance of a premature stop codon (p.Phe184Tyrfs*26) and likely a truncated protein. This result constitutes a new splice-site variant report in the PJVK gene leading to DFNB59 type associated with autosomal recessive non-syndromic hearing impairment (ARNSHI).
最近研究表明，PJVK基因会使人对声音产生高度易损性，它是首个因神经缺陷导致非综合征性听力损失的人类基因。对先证者进行了150多个已知耳聋基因的靶向二代测序。采用桑格测序法验证PJVK基因变异，并确认该疾病的家族遗传情况。已进行基于小基因的分析，以评估该变异对剪接的影响。我们在一名患有重度至极重度先天性耳聋的毛里塔尼亚儿童中，发现了PJVK基因纯合状态下一个新的c.550-6A＞G受体剪接位点变异。该替换位于第4内含子。小基因分析证实了该变异的影响，结果显示该变异（额外插入5个碱基对）产生了一个新的剪接位点，导致出现提前终止密码子（p.Phe184Tyrfs*26），可能产生截短蛋白。这一结果构成了PJVK基因一个新的剪接位点变异报告，导致与常染色体隐性非综合征性听力损失（ARNSHI）相关的DFNB59型。
