Whole Exome Sequencing Identifies Mutations in Usher Syndrome Genes in Profoundly Deaf Tunisian Patients

• DOI: 10.1371/journal.pone.0120584
• Publication Date: 2015-03-23T18:58:09Z
• Authors: Zied Riahi; Crystel Bonnet; Rim Zainine; Saida Lahbib; Yosra Bouyacoub; Rym Bechraoui; Jihène Marrakchi; Jean-Pierre Hardelin; Malek Louha; Leila Largueche; Salim Ben Yahia; Moncef Kheirallah; Leila Elmatri; Ghazi Besbes; Sonia Abdelhak; Christine Petit
• Keywords: Usher syndrome; Nonsense mutation; Disease gene identification

Usher syndrome (USH) is an autosomal recessive disorder characterized by combined deafness-blindness. It accounts for about 50% of all hereditary deafness blindness cases. Three clinical subtypes (USH1, USH2, and USH3) are described, which USH1 the most severe form, congenital profound deafness, constant vestibular dysfunction, a prepubertal onset retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected apparently isolated, with reportedly normal ocular fundus examination. Four biallelic mutations were identified two genes: splice acceptor site mutation, c.2283-1G>T, novel missense c.5434G>A (p.Glu1812Lys), MYO7A, previously unreported USH1G, i.e. frameshift c.1195_1196delAG (p.Leu399Alafs*24), nonsense c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed presence pigmentosa patients. Our findings provide evidence that USH under-diagnosed deaf Yet, early diagnosis utmost importance because these should undergo cochlear implant surgery childhood, anticipation visual loss.