Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. - Institut Pasteur Access content directly
Journal Articles Orphanet Journal of Rare Diseases Year : 2011

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

Sandrine Marlin
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  • PersonId : 906470
Marine Parodi
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  • PersonId : 919142
Magali Niasme-Grare
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  • PersonId : 919143
Diana Zelenika
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  • PersonId : 901771
Marc Délépine
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  • PersonId : 919144
Delphine Feldmann
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  • PersonId : 887760
Laurence Jonard
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  • PersonId : 919145
Bruno Delobel
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  • PersonId : 919148
Christophe Vincent
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  • PersonId : 919149
Hélène Dollfus
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  • PersonId : 907539
Albert David
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  • PersonId : 918889
Catherine Calais
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  • PersonId : 919151
Bettina Montaut-Verient
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  • PersonId : 919153
Jacques Dubin
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  • PersonId : 919155
Thierry Mom
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  • PersonId : 919157
Didier Lacombe
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  • PersonId : 886371
Françoise Duriez
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  • PersonId : 919158
Valérie Drouin-Garraud
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  • PersonId : 902580
Marie-Françoise Thuillier-Obstoy
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  • PersonId : 919159
Anne-Marie Frances
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  • PersonId : 919160
Patrick Collignon
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  • PersonId : 907536
Georges Challe
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  • PersonId : 919161
Rémy Couderc
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  • PersonId : 919162
Mark Lathrop
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  • PersonId : 919163
José-Alain Sahel
Jean Weissenbach
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  • PersonId : 911249

Abstract

BACKGROUND: Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. METHODS: We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). RESULTS: Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. CONCLUSIONS: Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

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Genetics
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Dates and versions

pasteur-00663885 , version 1 (27-01-2012)

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Crystel Bonnet, M'Hamed Grati, Sandrine Marlin, Jacqueline Levilliers, Jean-Pierre Hardelin, et al.. Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.. Orphanet Journal of Rare Diseases, 2011, 6 (1), pp.21. ⟨10.1186/1750-1172-6-21⟩. ⟨pasteur-00663885⟩
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