Titre :

DISP1 deficiency: monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.

Auteur(s) :

Lavillaureix, A. [Auteur]
Centre de référence Maladies Rares CLAD-Ouest [Rennes]
Rollier, P. [Auteur]
Hôpital Sud [CHU Rennes]
Kim, A. [Auteur]
Panasenkava, V. [Auteur]
De Tayrac, M. [Auteur]
Carré, W. [Auteur]
Guyodo, H. [Auteur]
Faoucher, M. [Auteur]
Poirel, E. [Auteur]
Akloul, L. [Auteur]
Quelin, C. [Auteur]
Whalen, S. [Auteur]
Bos, J. [Auteur]
Broekema, M. [Auteur]
Van Hagen, J. M. [Auteur]
Grand, K. [Auteur]
Allen-Sharpley, M. [Auteur]
Magness, E. [Auteur]
Mclean, S. [Auteur]
Kayserili, H. [Auteur]
Altunoglu, U. [Auteur]
En Qi Chong, A. [Auteur]
Xue, S. [Auteur]
Jeanne, M. [Auteur]
Almontashiri, N. [Auteur]
Habhab, W. [Auteur]
Vanlerberghe, Clemence [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Faivre, L. [Auteur]
Viora Dupont, E. [Auteur]
Philippe, C. [Auteur]
Safraou, H. [Auteur]
Laffargue, F. [Auteur]
Mittendorf, L. [Auteur]
Abou Jamra, R. [Auteur]
Patil, S. J. [Auteur]
Dalal, A. [Auteur]
Sarma, A. S. [Auteur]
Keren, B. [Auteur]
Reversade, B. [Auteur]
Dubourg, C. [Auteur]
Odent, S. [Auteur]
Dupé, V. [Auteur]
Institut de Génétique et Développement de Rennes [IGDR]

Titre de la revue :

Genetics in Medicine

Nom court de la revue :

Genet Med

Numéro :

26

Pagination :

101126

Date de publication :

2024-04-10

ISSN :

1530-0366

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Purpose: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and ...
Lire la suite >Purpose: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with division transporter dispatched-1 (DISP1) variants. Methods: This study was based on the identification of at least 1 pathogenic variant of the DISP1 gene in individuals for whom detailed clinical data were available. Results: A total of 23 DISP1 variants were identified in heterozygous, compound heterozygous or homozygous states in 25 individuals with midline craniofacial defects. Most cases were minor forms of HPE, with craniofacial features such as orofacial cleft, solitary median maxillary central incisor, and congenital nasal pyriform aperture stenosis. These individuals had either monoallelic loss-of-function variants or biallelic missense variants in DISP1. In individuals with severe HPE, the DISP1 variants were commonly found associated with a variant in another HPE-linked gene (ie, oligogenic inheritance). Conclusion: The genetic findings we have acquired demonstrate a significant involvement of DISP1 variants in the phenotypic spectrum of midline defects. This underlines its importance as a crucial element in the efficient secretion of Sonic hedgehog. We also demonstrated that the very rare solitary median maxillary central incisor and congenital nasal pyriform aperture stenosis combination is part of the DISP1-related phenotype. The present study highlights the clinical risks to be flagged up during genetic counseling after the discovery of a pathogenic DISP1 variant .Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

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

Date de dépôt :

2024-05-06T23:16:04Z
2024-06-19T10:12:48Z