Title :

Evaluation of somatic and/or germline mosaicism in congenital malformation of the eye

Author(s) :

Chesneau, Bertrand [Auteur]
Service Génétique Médicale [CHU Toulouse]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
Ivashchenko, Véronique [Auteur]
Service Génétique Médicale [CHU Toulouse]
Habib, Christophe [Auteur]
Service Génétique Médicale [CHU Toulouse]
Gaston, Véronique [Auteur]
Service Génétique Médicale [CHU Toulouse]
Escudié, Fréderic [Auteur]
Service Anatomie et cytologie pathologiques [CHU Toulouse]
Morel, Godelieve [Auteur]
Centre Hospitalier Universitaire [Rennes]
Capri, Yline [Auteur]
Département de génétique [Robert Debré]
Vincent, Catherine [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Calvas, Patrick [Auteur]
Service Génétique Médicale [CHU Toulouse]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
Chassaing, Nicolas [Auteur]
Service Génétique Médicale [CHU Toulouse]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale
Plaisancié, Julie [Auteur]
Université Toulouse III - Paul Sabatier [UT3]
Service Génétique Médicale [CHU Toulouse]
Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale

Journal title :

European Journal of Human Genetics

Abbreviated title :

Eur J Hum Genet

Volume number :

31

Pages :

526–530

Publisher :

Nature Publishing Group

Publication date :

2022-11-21

ISSN :

1476-5438

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Microphthalmia, Anophthalmia and Coloboma (MAC) form a spectrum of congenital eye malformations responsible for severe visual impairment. Despite the exploration of hundreds of genes by High-Throughput Sequencing (HTS), ...
Show more >Microphthalmia, Anophthalmia and Coloboma (MAC) form a spectrum of congenital eye malformations responsible for severe visual impairment. Despite the exploration of hundreds of genes by High-Throughput Sequencing (HTS), most of the patients remain without genetic diagnosis. One explanation could be the not yet demonstrated involvement of somatic mosaicism (undetected by conventional analysis pipelines) in those patients. Furthermore, the proportion of parental germline mosaicism in presumed de novo variations is still unknown in ocular malformations. Thus, using dedicated bioinformatics pipeline designed to detect mosaic variants, we reanalysed the sequencing data obtained from a 119 ocular development genes panel performed on blood samples of 78 probands with sporadic MAC without genetic diagnosis. Using the same HTS strategy, we sequenced 80 asymptomatic parents of 41 probands carrying a disease-causing variant in an ocular development gene considered de novo after Sanger sequencing of both parents. Reanalysis of the previously sequencing data did not find any mosaic variant in probands without genetic diagnosis. However, HTS of parents revealed undetected SOX2 and PAX6 mosaic variants in two parents. Finally, this work, performed on two large cohorts of patients with MAC spectrum, provides for the first time an overview of the interest of looking for mosaicism in ocular development disorders. Somatic mosaicism does not appear to be frequent in MAC spectrum and might explain only few diagnoses. Thus, other approaches such as whole genome sequencing should be considered in those patients. Parental mosaicism is however not that rare (around 5%) and challenging for genetic counselling.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

ANR Project :

Cohorte nationale maladies rares

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2024-06-25T21:35:52Z
2024-10-29T12:51:40Z