Non-USH2A mutations in USH2 patients.

Thomas Besnard; Christel Vaché; David Baux; Lise Larrieu; Caroline Abadie; Catherine Blanchet; Sylvie Odent; Patricia Blanchet; Patrick Calvas; Christian Hamel; Hélène Dollfus; Geneviève Lina-Granade; James Lespinasse; Albert David; Bertrand Isidor; Gilles Morin; Sue Malcolm; Sylvie Tuffery-Giraud; Mireille Claustres; Anne-Françoise Roux

doi:10.1002/humu.22004

Journal articles

Non-USH2A mutations in USH2 patients.

Thomas Besnard ¹ Christel Vaché ¹ David Baux ¹ Lise Larrieu ¹ Caroline Abadie ¹ Catherine Blanchet ² Sylvie Odent ³ Patricia Blanchet ⁴ Patrick Calvas ⁵ Christian Hamel ² Hélène Dollfus ⁶ Geneviève Lina-Granade ⁷ James Lespinasse ⁸ Albert David ⁹ Bertrand Isidor ⁹ Gilles Morin ¹⁰ Sue Malcolm ¹¹ Sylvie Tuffery-Giraud ¹ Mireille Claustres ¹ Anne-Françoise Roux ^{1, *}

* Corresponding author

1 LGMR - Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques

2 Centre de référence des affections sensorielles d'origine génétique

3 Service de génétique clinique [Rennes]

4 Unité de Génétique Médicale et Foetopathologie

5 Service de génétique médicale

6 Service de Génétique Médicale

7 Département d'ORL, chirurgie cervico-maxillo-faciale et d'audiophonologie [Hôpital Edouard Herriot - HCL]

8 Département de Génétique Chromosomique

9 Service de génétique médicale - Unité de génétique clinique [Nantes]

10 Service de génétique médicale

11 Clinical and Molecular Genetics

Abstract : We have systematically analyzed the two known minor genes involved in Usher syndrome type 2, DFNB31 and GPR98, for mutations in a cohort of 31 patients not linked to USH2A. PDZD7, an Usher syndrome type 2 (USH2) related gene, was analyzed when indicated. We found that mutations in GPR98 contribute significantly to USH2. We report 17 mutations in 10 individuals, doubling the number of GPR98 mutations reported to date. In contrast to mutations in usherin, the mutational spectrum of GPR98 predominantly results in a truncated protein product. This is true even when the mutation affects splicing, and we have incorporated a splicing reporter minigene assay to show this, where appropriate. Only two mutations were found which we believe to be genuine missense changes. Discrepancy in the mutational spectrum between GPR98 and USH2A is discussed. Only two patients were found with mutations in DFNB31, showing that mutations of this gene contribute to only a very small extent to USH2. Close examination of the clinical details, where available, for patients in whom no mutation was found in USH2A, GPR98, or DFNB31, showed that most of them had atypical features. In effect, these three genes account for the vast majority of USH2 patients and their analysis provide a robust pathway for routine molecular diagnosis.

Keywords : Usher syndrome GPR98 DFNB31 functional analysis molecular analysis

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics

Life Sciences [q-bio] / Human health and pathology / Sensory Organs

Complete list of metadatas

https://www.hal.inserm.fr/inserm-00650795
Contributor : Hervé de Villemeur <>
Submitted on : Monday, December 12, 2011 - 11:58:24 AM
Last modification on : Friday, May 15, 2020 - 12:22:04 PM

Non-USH2A mutations in USH2 patients.

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Non-USH2A mutations in USH2 patients.

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