title: Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome.
abstract: Usher syndrome (USH) is an autosomal recessive disorder characterized by a dual sensory impairment affecting hearing and vision. USH is clinically and genetically heterogeneous. Ten different causal genes have been reported. We studied the molecular bases of the disease in 18 unrelated Algerian patients by targeted-exome sequencing, and identified the causal biallelic mutations in all of them: 16 patients carried the mutations at the homozygous state and 2 at the compound heterozygous state. Nine of the 17 different mutations detected in MYO7A (1 of 5 mutations), CDH23 (4 of 7 mutations), PCDH15 (1 mutation), USH1C (1 mutation), USH1G (1 mutation), and USH2A (1 of 2 mutations), had not been previously reported. The deleterious consequences of a missense mutation of CDH23 (p.Asp1501Asn) and the in-frame single codon deletion in USH1G (p.Ala397del) on the corresponding proteins were predicted from the solved 3D-structures of extracellular cadherin (EC) domains of cadherin-23 and the sterile alpha motif (SAM) domain of USH1G/sans, respectively. In addition, we were able to show that the USH1G mutation is likely to affect the binding interface between the SAM domain and USH1C/harmonin. This should spur the use of 3D-structures, not only of isolated protein domains, but also of protein-protein interaction interfaces, to predict the functional impact of mutations detected in the USH genes.
authors: Laboratoire de biochimie génétique, Service de biologie - CHU de Bab El Oued, Université d'Alger 1, 16 Alger, Algérie.|Laboratoire central de biologie, CHU Frantz Fanon, 09 Blida, Algérie.|Faculté de médecine, Université Saad Dahleb, 09 Blida, Algérie.
authors: Samia
authors: S
authors: Abdi
authors: Unité de génétique et physiologie de l'audition, INSERM UMRS1120, Institut Pasteur, 75015, Paris, France.
authors: Amel
authors: A
authors: Bahloul
authors: Laboratoire de biochimie génétique, Service de biologie - CHU de Bab El Oued, Université d'Alger 1, 16 Alger, Algérie.|Faculté des sciences biologiques, Université des sciences et de la technologie Houari Boumédiène, 16 Alger, Algérie.
authors: Asma
authors: A
authors: Behlouli
authors: Unité de génétique et physiologie de l'audition, INSERM UMRS1120, Institut Pasteur, 75015, Paris, France.
authors: Jean-Pierre
authors: JP
authors: Hardelin
authors: Laboratoire de biochimie génétique, Service de biologie - CHU de Bab El Oued, Université d'Alger 1, 16 Alger, Algérie.
authors: Mohamed
authors: M
authors: Makrelouf
authors: Faculté de médecine, Université Saad Dahleb, 09 Blida, Algérie.|Service d'ophtalmologie, CHU Frantz Fanon, 09 Blida, Algérie.
authors: Kamel
authors: K
authors: Boudjelida
authors: Service de biochimie et de biologie moléculaire, Hôpital Armand Trousseau, APHP, 75012, Paris, France.
authors: Malek
authors: M
authors: Louha
authors: Faculté de médecine, Université Saad Dahleb, 09 Blida, Algérie.|Service d'ORL, CHU Frantz Fanon, 09 Blida, Algérie.
authors: Ahmed
authors: A
authors: Cheknene
authors: Laboratoire central de biologie, CHU Frantz Fanon, 09 Blida, Algérie.|Faculté de médecine, Université Saad Dahleb, 09 Blida, Algérie.
authors: Rachid
authors: R
authors: Belouni
authors: Faculté de médecine, Université Saad Dahleb, 09 Blida, Algérie.|Service d'ORL, CHU Frantz Fanon, 09 Blida, Algérie.
authors: Yahia
authors: Y
authors: Rous
authors: Faculté de médecine, Université Saad Dahleb, 09 Blida, Algérie.|Service d'ophtalmologie, CHU Frantz Fanon, 09 Blida, Algérie.
authors: Zahida
authors: Z
authors: Merad
authors: Service d'ORL, CHU Bab el Oued, 16 Alger, Algérie.
authors: Djamel
authors: D
authors: Selmane
authors: Service d'ORL, CHU Tizi Ouzou, 15 Tizi-Ouzou, Algérie.
authors: Mokhtar
authors: M
authors: Hasbelaoui
authors: INSERM UMRS 1120, Institut de la vision, Université Pierre et Marie Curie, 75005, Paris, France.
authors: Crystel
authors: C
authors: Bonnet
authors: Laboratoire de biochimie génétique, Service de biologie - CHU de Bab El Oued, Université d'Alger 1, 16 Alger, Algérie.
authors: Akila
authors: A
authors: Zenati
authors: Unité de génétique et physiologie de l'audition, INSERM UMRS1120, Institut Pasteur, 75015, Paris, France.|INSERM UMRS 1120, Institut de la vision, Université Pierre et Marie Curie, 75005, Paris, France.|Collège de France, 75005, Paris, France.
authors: Christine
authors: C
authors: Petit
mesh_terms: D000462:Algeria; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D020125:Mutation, Missense; D052245:Usher Syndromes / Q000235:genetics*