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Identification of candidate regions for a novel Usher syndrome type II locus

PURPOSE: Chronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during pub...

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Autores principales: Ben Rebeh, Imen, Benzina, Zeineb, Dhouib, Houria, Hadjamor, Imen, Amyere, Mustapha, Ayadi, Leila, Turki, Khalil, Hammami, Bouthaina, Kmiha, Noureddine, Kammoun, Hassen, Hakim, Bochra, Charfedine, Ilhem, Vikkula, Miikka, Ghorbel, Abdelmonem, Ayadi, Hammadi, Masmoudi, Saber
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538493/
https://www.ncbi.nlm.nih.gov/pubmed/18806881
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author Ben Rebeh, Imen
Benzina, Zeineb
Dhouib, Houria
Hadjamor, Imen
Amyere, Mustapha
Ayadi, Leila
Turki, Khalil
Hammami, Bouthaina
Kmiha, Noureddine
Kammoun, Hassen
Hakim, Bochra
Charfedine, Ilhem
Vikkula, Miikka
Ghorbel, Abdelmonem
Ayadi, Hammadi
Masmoudi, Saber
author_facet Ben Rebeh, Imen
Benzina, Zeineb
Dhouib, Houria
Hadjamor, Imen
Amyere, Mustapha
Ayadi, Leila
Turki, Khalil
Hammami, Bouthaina
Kmiha, Noureddine
Kammoun, Hassen
Hakim, Bochra
Charfedine, Ilhem
Vikkula, Miikka
Ghorbel, Abdelmonem
Ayadi, Hammadi
Masmoudi, Saber
author_sort Ben Rebeh, Imen
collection PubMed
description PURPOSE: Chronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to severe hearing impairment with downsloping pure-tone audiogram, and normal vestibular function. Four loci and three genes are known for USH2. In this study, we proposed to localize the gene responsible for USH2 in a consanguineous family of Tunisian origin. METHODS: Affected members underwent detailed ocular and audiologic characterization. One Tunisian family with USH2 and 45 healthy controls unrelated to the family were recruited. Two affected and six unaffected family members attended our study. DNA samples of eight family members were genotyped with polymorphic markers. Two-point and multipoint LOD scores were calculated using Genehunter software v2.1. Sequencing was used to investigate candidate genes. RESULTS: Haplotype analysis showed no significant linkage to any known USH gene or locus. A genome-wide screen, using microsatellite markers, was performed, allowing the identification of three homozygous regions in chromosomes 2, 4, and 15. We further confirmed and refined these three regions using microsatellite and single-nucleotide polymorphisms. With recessive mode of inheritance, the highest multipoint LOD score of 1.765 was identified for the candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55 Mb), underscoring the limited number of meioses in the consanguineous pedigree. Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data strongly suggest that the novel locus for USH2 is likely to reside on 15q. CONCLUSIONS: Our data provide a basis for the localization and the identification of a novel gene implicated in USH2, most likely localized on 15q.
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spelling pubmed-25384932008-09-21 Identification of candidate regions for a novel Usher syndrome type II locus Ben Rebeh, Imen Benzina, Zeineb Dhouib, Houria Hadjamor, Imen Amyere, Mustapha Ayadi, Leila Turki, Khalil Hammami, Bouthaina Kmiha, Noureddine Kammoun, Hassen Hakim, Bochra Charfedine, Ilhem Vikkula, Miikka Ghorbel, Abdelmonem Ayadi, Hammadi Masmoudi, Saber Mol Vis Research Article PURPOSE: Chronic diseases affecting the inner ear and the retina cause severe impairments to our communication systems. In more than half of the cases, Usher syndrome (USH) is the origin of these double defects. Patients with USH type II (USH2) have retinitis pigmentosa (RP) that develops during puberty, moderate to severe hearing impairment with downsloping pure-tone audiogram, and normal vestibular function. Four loci and three genes are known for USH2. In this study, we proposed to localize the gene responsible for USH2 in a consanguineous family of Tunisian origin. METHODS: Affected members underwent detailed ocular and audiologic characterization. One Tunisian family with USH2 and 45 healthy controls unrelated to the family were recruited. Two affected and six unaffected family members attended our study. DNA samples of eight family members were genotyped with polymorphic markers. Two-point and multipoint LOD scores were calculated using Genehunter software v2.1. Sequencing was used to investigate candidate genes. RESULTS: Haplotype analysis showed no significant linkage to any known USH gene or locus. A genome-wide screen, using microsatellite markers, was performed, allowing the identification of three homozygous regions in chromosomes 2, 4, and 15. We further confirmed and refined these three regions using microsatellite and single-nucleotide polymorphisms. With recessive mode of inheritance, the highest multipoint LOD score of 1.765 was identified for the candidate regions on chromosomes 4 and 15. The chromosome 15 locus is large (55 Mb), underscoring the limited number of meioses in the consanguineous pedigree. Moreover, the linked, homozygous chromosome 15q alleles, unlike those of the chromosome 2 and 4 loci, are infrequent in the local population. Thus, the data strongly suggest that the novel locus for USH2 is likely to reside on 15q. CONCLUSIONS: Our data provide a basis for the localization and the identification of a novel gene implicated in USH2, most likely localized on 15q. Molecular Vision 2008-09-19 /pmc/articles/PMC2538493/ /pubmed/18806881 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Ben Rebeh, Imen
Benzina, Zeineb
Dhouib, Houria
Hadjamor, Imen
Amyere, Mustapha
Ayadi, Leila
Turki, Khalil
Hammami, Bouthaina
Kmiha, Noureddine
Kammoun, Hassen
Hakim, Bochra
Charfedine, Ilhem
Vikkula, Miikka
Ghorbel, Abdelmonem
Ayadi, Hammadi
Masmoudi, Saber
Identification of candidate regions for a novel Usher syndrome type II locus
title Identification of candidate regions for a novel Usher syndrome type II locus
title_full Identification of candidate regions for a novel Usher syndrome type II locus
title_fullStr Identification of candidate regions for a novel Usher syndrome type II locus
title_full_unstemmed Identification of candidate regions for a novel Usher syndrome type II locus
title_short Identification of candidate regions for a novel Usher syndrome type II locus
title_sort identification of candidate regions for a novel usher syndrome type ii locus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538493/
https://www.ncbi.nlm.nih.gov/pubmed/18806881
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