title: Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients.
abstract: 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, of which USH1 is the most severe form, characterized by congenital profound deafness, constant vestibular dysfunction, and a prepubertal onset of retinitis pigmentosa. We performed whole exome sequencing in four unrelated Tunisian patients affected by apparently isolated, congenital profound deafness, with reportedly normal ocular fundus examination. Four biallelic mutations were identified in two USH1 genes: a splice acceptor site mutation, c.2283-1G>T, and a novel missense mutation, c.5434G>A (p.Glu1812Lys), in MYO7A, and two previously unreported mutations in USH1G, i.e. a frameshift mutation, c.1195_1196delAG (p.Leu399Alafs*24), and a nonsense mutation, c.52A>T (p.Lys18*). Another ophthalmological examination including optical coherence tomography actually showed the presence of retinitis pigmentosa in all the patients. Our findings provide evidence that USH is under-diagnosed in Tunisian deaf patients. Yet, early diagnosis of USH is of utmost importance because these patients should undergo cochlear implant surgery in early childhood, in anticipation of the visual loss.
authors: Institut Pasteur de Tunis, LR11IPT05, Biomedical Genomics and Oncogenetics Laboratory, 1002, Tunis, Tunisia; Faculté des Sciences de Tunis, Université de Tunis El Manar, 2092 El Manar I Tunis, Tunis, Tunisia.
authors: Zied
authors: Z
authors: Riahi
authors: Institut de la Vision, INSERM UMRS 1120, UPMC- Paris 6, Paris, France.
authors: Crystel
authors: C
authors: Bonnet
authors: La Rabta Hospital, Otorhinolaryngology Diseases, Tunis, Tunisia.
authors: Rim
authors: R
authors: Zainine
authors: Institut Pasteur de Tunis, LR11IPT05, Biomedical Genomics and Oncogenetics Laboratory, 1002, Tunis, Tunisia.
authors: Saida
authors: S
authors: Lahbib
authors: Institut Pasteur de Tunis, LR11IPT05, Biomedical Genomics and Oncogenetics Laboratory, 1002, Tunis, Tunisia; Université de Monastir, Institut Supérieur de Biotechnologie, Monastir, Tunisia.
authors: Yosra
authors: Y
authors: Bouyacoub
authors: La Rabta Hospital, Otorhinolaryngology Diseases, Tunis, Tunisia.
authors: Rym
authors: R
authors: Bechraoui
authors: La Rabta Hospital, Otorhinolaryngology Diseases, Tunis, Tunisia.
authors: Jihène
authors: J
authors: Marrakchi
authors: Institut Pasteur, Unité de Génétique et Physiologie de l'Audition, Paris, France.
authors: Jean-Pierre
authors: JP
authors: Hardelin
authors: Laboratoire de Biochimie et de Biologie Moléculaire, Hôpital Armand Trousseau, APHP, Paris, France.
authors: Malek
authors: M
authors: Louha
authors: Department B of Ophthalmology, Hedi Rais Institute of Ophthalmology, Tunis, Tunisia.
authors: Leila
authors: L
authors: Largueche
authors: Universite de Monastir, Faculty of Medicine, Fattouma Bourguiba University Hospital, Department of Ophthalmology, 5000, Monastir, Tunisia.
authors: Salim
authors: S
authors: Ben Yahia
authors: Universite de Monastir, Faculty of Medicine, Fattouma Bourguiba University Hospital, Department of Ophthalmology, 5000, Monastir, Tunisia.
authors: Moncef
authors: M
authors: Kheirallah
authors: Department B of Ophthalmology, Hedi Rais Institute of Ophthalmology, Tunis, Tunisia.
authors: Leila
authors: L
authors: Elmatri
authors: La Rabta Hospital, Otorhinolaryngology Diseases, Tunis, Tunisia.
authors: Ghazi
authors: G
authors: Besbes
authors: Institut Pasteur de Tunis, LR11IPT05, Biomedical Genomics and Oncogenetics Laboratory, 1002, Tunis, Tunisia.
authors: Sonia
authors: S
authors: Abdelhak
authors: Institut de la Vision, INSERM UMRS 1120, UPMC- Paris 6, Paris, France; Institut Pasteur, Unité de Génétique et Physiologie de l'Audition, Paris, France; Collège de France, Paris, France.
authors: Christine
authors: C
authors: Petit
mesh_terms: D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D003638:Deafness / Q000235:genetics*; D059472:Exome; D005190:Family; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D009218:Myosins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000378:metabolism / Q000473:pathology; D014416:Tunisia
chemical_list: D017630:Connexins; D000072259:Connexin 26; D009218:Myosins