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

Crystel Bonnet, M'Hamed Grati, Sandrine Marlin, Jacqueline Levilliers, Jean Pierre Hardelin, Marine Parodi, Magali Niasme-Grare, Diana Zelenika, Marc Délépine, Delphine Feldmann, Laurence Jonard, Aziz El-Amraoui, Dominique Weil, Bruno Delobel, Christophe Vincent, Hélène Dollfus, Marie Madeleine Eliot, Albert David, Catherine Calais, Jacqueline VigneronBettina Montaut-Verient, Dominique Bonneau, Jacques Dubin, Christel Thauvin, Alain Duvillard, Christine Francannet, Thierry Mom, Didier Lacombe, Françoise Duriez, Valérie Drouin-Garraud, Marie Françoise Thuillier-Obstoy, Sabine Sigaudy, Anne Marie Frances, Patrick Collignon, Georges Challe, Rémy Couderc, Mark Lathrop, José Alain Sahel, Jean Weissenbach, Christine Petit, Françoise Denoyelle

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


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.

Original languageEnglish (US)
Article number21
JournalOrphanet journal of rare diseases
Issue number1
StatePublished - 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)


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