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 journalArticle

64 Citations (Scopus)

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.

Original languageEnglish (US)
Article number21
JournalOrphanet Journal of Rare Diseases
Volume6
Issue number1
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

Usher Syndromes
Exons
Mutation
Genes
Deaf-Blind Disorders
Genetic Counseling
Genetic Therapy
Early Diagnosis

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

Bonnet, C., Grati, MH., Marlin, S., Levilliers, J., Hardelin, J. P., Parodi, M., ... Denoyelle, F. (2011). Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. Orphanet Journal of Rare Diseases, 6(1), [21]. https://doi.org/10.1186/1750-1172-6-21

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

In: Orphanet Journal of Rare Diseases, Vol. 6, No. 1, 21, 2011.

Research output: Contribution to journalArticle

Bonnet, C, Grati, MH, Marlin, S, Levilliers, J, Hardelin, JP, Parodi, M, Niasme-Grare, M, Zelenika, D, Délépine, M, Feldmann, D, Jonard, L, El-Amraoui, A, Weil, D, Delobel, B, Vincent, C, Dollfus, H, Eliot, MM, David, A, Calais, C, Vigneron, J, Montaut-Verient, B, Bonneau, D, Dubin, J, Thauvin, C, Duvillard, A, Francannet, C, Mom, T, Lacombe, D, Duriez, F, Drouin-Garraud, V, Thuillier-Obstoy, MF, Sigaudy, S, Frances, AM, Collignon, P, Challe, G, Couderc, R, Lathrop, M, Sahel, JA, Weissenbach, J, Petit, C & Denoyelle, F 2011, 'Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis', Orphanet Journal of Rare Diseases, vol. 6, no. 1, 21. https://doi.org/10.1186/1750-1172-6-21
Bonnet, Crystel ; Grati, M'Hamed ; Marlin, Sandrine ; Levilliers, Jacqueline ; Hardelin, Jean Pierre ; Parodi, Marine ; Niasme-Grare, Magali ; Zelenika, Diana ; Délépine, Marc ; Feldmann, Delphine ; Jonard, Laurence ; El-Amraoui, Aziz ; Weil, Dominique ; Delobel, Bruno ; Vincent, Christophe ; Dollfus, Hélène ; Eliot, Marie Madeleine ; David, Albert ; Calais, Catherine ; Vigneron, Jacqueline ; Montaut-Verient, Bettina ; Bonneau, Dominique ; Dubin, Jacques ; Thauvin, Christel ; Duvillard, Alain ; Francannet, Christine ; Mom, Thierry ; Lacombe, Didier ; Duriez, Françoise ; Drouin-Garraud, Valérie ; Thuillier-Obstoy, Marie Françoise ; Sigaudy, Sabine ; Frances, Anne Marie ; Collignon, Patrick ; Challe, Georges ; Couderc, Rémy ; Lathrop, Mark ; Sahel, José Alain ; Weissenbach, Jean ; Petit, Christine ; Denoyelle, Françoise. / Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. In: Orphanet Journal of Rare Diseases. 2011 ; Vol. 6, No. 1.
@article{e082c5138c1e440f8c0f29342f0945d4,
title = "Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis",
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.",
author = "Crystel Bonnet and M'Hamed Grati and Sandrine Marlin and Jacqueline Levilliers and Hardelin, {Jean Pierre} and Marine Parodi and Magali Niasme-Grare and Diana Zelenika and Marc D{\'e}l{\'e}pine and Delphine Feldmann and Laurence Jonard and Aziz El-Amraoui and Dominique Weil and Bruno Delobel and Christophe Vincent and H{\'e}l{\`e}ne Dollfus and Eliot, {Marie Madeleine} and Albert David and Catherine Calais and Jacqueline Vigneron and Bettina Montaut-Verient and Dominique Bonneau and Jacques Dubin and Christel Thauvin and Alain Duvillard and Christine Francannet and Thierry Mom and Didier Lacombe and Fran{\cc}oise Duriez and Val{\'e}rie Drouin-Garraud and Thuillier-Obstoy, {Marie Fran{\cc}oise} and Sabine Sigaudy and Frances, {Anne Marie} and Patrick Collignon and Georges Challe and R{\'e}my Couderc and Mark Lathrop and Sahel, {Jos{\'e} Alain} and Jean Weissenbach and Christine Petit and Fran{\cc}oise Denoyelle",
year = "2011",
doi = "10.1186/1750-1172-6-21",
language = "English (US)",
volume = "6",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

AU - Bonnet, Crystel

AU - Grati, M'Hamed

AU - Marlin, Sandrine

AU - Levilliers, Jacqueline

AU - Hardelin, Jean Pierre

AU - Parodi, Marine

AU - Niasme-Grare, Magali

AU - Zelenika, Diana

AU - Délépine, Marc

AU - Feldmann, Delphine

AU - Jonard, Laurence

AU - El-Amraoui, Aziz

AU - Weil, Dominique

AU - Delobel, Bruno

AU - Vincent, Christophe

AU - Dollfus, Hélène

AU - Eliot, Marie Madeleine

AU - David, Albert

AU - Calais, Catherine

AU - Vigneron, Jacqueline

AU - Montaut-Verient, Bettina

AU - Bonneau, Dominique

AU - Dubin, Jacques

AU - Thauvin, Christel

AU - Duvillard, Alain

AU - Francannet, Christine

AU - Mom, Thierry

AU - Lacombe, Didier

AU - Duriez, Françoise

AU - Drouin-Garraud, Valérie

AU - Thuillier-Obstoy, Marie Françoise

AU - Sigaudy, Sabine

AU - Frances, Anne Marie

AU - Collignon, Patrick

AU - Challe, Georges

AU - Couderc, Rémy

AU - Lathrop, Mark

AU - Sahel, José Alain

AU - Weissenbach, Jean

AU - Petit, Christine

AU - Denoyelle, Françoise

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79955761322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955761322&partnerID=8YFLogxK

U2 - 10.1186/1750-1172-6-21

DO - 10.1186/1750-1172-6-21

M3 - Article

C2 - 21569298

AN - SCOPUS:79955761322

VL - 6

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

IS - 1

M1 - 21

ER -