Titre :

Whole exome sequencing identifies mutations in 10% of patients with familial non-syndromic cleft lip and/or palate in genes mutated in well-known syndromes

Auteur(s) :

Basha, Mirta [Auteur]
Demeer, Benedicte [Auteur]
Revencu, Nicole [Auteur]
Helaers, Raphael [Auteur]
Theys, Stephanie [Auteur]
Bou Saba, Sami [Auteur]
Boute, Odile [Auteur]
Devauchelle, Bernard [Auteur]
Francois, Genevieve [Auteur]
Bayet, Benedicte [Auteur]
Vikkula, Miikka [Auteur]

Titre de la revue :

Journal of medical genetics

Nom court de la revue :

J. Med. Genet.

Date de publication :

2018-03-02

ISSN :

1468-6244

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Oral clefts, that is, clefts of the lip and/or cleft palate (CL/P), are the most common craniofacial birth defects with an approximate incidence of ~1/700. To date, physicians stratify patients with oral clefts into either ...
Lire la suite >Oral clefts, that is, clefts of the lip and/or cleft palate (CL/P), are the most common craniofacial birth defects with an approximate incidence of ~1/700. To date, physicians stratify patients with oral clefts into either syndromic CL/P (syCL/P) or non-syndromic CL/P (nsCL/P) depending on whether the CL/P is associated with another anomaly or not. In general, patients with syCL/P follow Mendelian inheritance, while those with nsCL/P have a complex aetiology and, as such, do not adhere to Mendelian inheritance. Genome-wide association studies have identified approximately 30 risk loci for nsCL/P, which could explain a small fraction of heritability. To identify variants causing nsCL/P, we conducted whole exome sequencing on 84 individuals with nsCL/P, drawn from multiplex families (n=46). We identified rare damaging variants in four genes known to be mutated in syCL/P: TP63TBX1LRP6GRHL3 These data demonstrate that patients with CL/P without cardinal signs of a syndrome may still carry a mutation in a gene linked to syCL/P. Rare coding and non-coding variants in syCL/P genes could in part explain the controversial question of 'missing heritability' for nsCL/P. Therefore, gene panels designed for diagnostic testing of syCL/P should be used for patients with nsCL/P, especially when there is at least third-degree family history. This would allow a more precise management, follow-up and genetic counselling. Moreover, stratified cohorts would allow hunting for genetic modifiers.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille

Collections :

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

Date de dépôt :

2021-09-02T07:01:13Z