Unité de Recherche sur les Biomarqueurs dans la Population Mauritanienne, UNA-FST, Nouakchott, Mauritania.
Institut de l'AuditionInstitut Pasteur, Inserm, Paris, France.
Eur Arch Otorhinolaryngol. 2023 Sep;280(9):4057-4063. doi: 10.1007/s00405-023-07907-z. Epub 2023 Mar 16.
Although recessive mutations in GJB2 are the common genetic etiology of sensorineural hearing impairment (SNHI), variants in LRTOMT gene were also identified, mostly in Middle East and North African populations.
Using Sanger sequencing we screened the exon 7 of LRTOMT in a cohort of 128 unrelated Mauritanian children with congenital deafness.
Only one biallelic missense mutation, predicted as pathogenic (c.179 T > C;p.Leu60Pro) was found at homozygous state in four families. This variant, not reported before, showed a deleterious effect by SIFT (score: 0.01) and a disease-causing effect by Mutation Taster (prob: 1). Exploration of the encoded protein 3D structure revealed a disruption from an organized α helix (in the normal protein structure) into a random conformation. Early fitting of a cochlear implant seemed to improve the audition ability of the mutation carrier.
Further screening using a panel of deafness genes may expose other variants underlying hearing impairment in our population.
尽管 GJB2 中的隐性突变是感音神经性听力损失（SNHI）的常见遗传病因，但也在中东和北非人群中发现了 LRTOMT 基因的变体。
我们使用 Sanger 测序法对 128 名无亲缘关系的毛里塔尼亚先天性耳聋儿童进行了 LRTOMT 外显子 7 的筛查。
在四个家庭中，发现了一种纯合子的错义突变，该突变预测为致病性的（c.179T>C;p.Leu60Pro）。该变体以前没有报道过，其 SIFT 评分（0.01）显示为有害，Mutation Taster（prob:1）显示为致病变异。对编码蛋白的 3D 结构的探索表明，该蛋白从有序的α螺旋（在正常蛋白结构中）变成了无规则的构象。早期植入人工耳蜗似乎可以提高突变携带者的听力能力。
进一步使用一组耳聋基因进行筛查可能会揭示我们人群中导致听力损失的其他变体。
