Title :

Exome sequencing identifies the first genetic determinants of sirenomelia in human

Author(s) :

Lecoquierre, Francois [Auteur]
Brehin, Anne-Claire [Auteur]
Coutant, Sophie [Auteur]
Coursimault, Juliette [Auteur]
Bazin, Anne [Auteur]
Centre d'Etudes et de Recherches Administratives, Politiques et Sociales - UMR 8026 [CERAPS]
Finck, Wilfrid [Auteur]
Benoist, Guillaume [Auteur]
Begorre, Marianne [Auteur]
Beneteau, Claire [Auteur]
Cailliez, Daniel [Auteur]
Chenal, Pierre [Auteur]
De Jong, Mirjam [Auteur]
Degre, Sophie [Auteur]
Devisme, Louise [Auteur]
Francannet, Christine [Auteur]
Gerard, Benedicte [Auteur]
Jeanne, Corinne [Auteur]
Joubert, Madeleine [Auteur]
Journel, Hubert [Auteur]
Laurichesse Delmas, Helene [Auteur]
Layet, Valerie [Auteur]
Liquier, Alain [Auteur]
Mangione, Raphaele [Auteur]
Patrier, Sophie [Auteur]
Pelluard, Fanny [Auteur]
Petit, Florence [Auteur]
Tillouche, Nadia [Auteur]
Van Ravenswaaij-Arts, Conny [Auteur]
Frebourg, Thierry [Auteur]
Saugier-Veber, Pascale [Auteur]
Gruchy, Nicolas [Auteur]
Nicolas, Gael [Auteur]
Gerard, Marion [Auteur]

Journal title :

Human mutation

Abbreviated title :

Hum. Mutat.

Publication date :

2020-02-14

ISSN :

1098-1004

Keyword(s) :

de novo mutation
Sirenomelia
exome sequencing
caudal dysgenesis
CDX2

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia ...
Show more >Sirenomelia is a rare severe malformation sequence of unknown cause characterized by fused legs and severe visceral abnormalities. We present a series of nine families including two rare familial aggregations of sirenomelia investigated by a trio-based exome sequencing strategy. This approach identified CDX2 variants in the two familial aggregations, both fitting an autosomal dominant pattern of inheritance with variable expressivity. CDX2 is a major regulator of caudal development in vertebrate and mouse heterozygotes are a previously described model of sirenomelia. Remarkably, the p.(Arg237His) variant has already been reported in a patient with persistent cloaca. Analysis of the sporadic cases revealed six additional candidate variants including a de novo frameshift variant in the genetically constrained NKD1 gene, encoding a known interactor of CDX2. We provide the first insights for a genetic contribution in human sirenomelia and highlight the role of Cdx and Wnt signaling pathways in the development of this disorder.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille

Collections :

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

Submission date :

2021-09-02T07:02:22Z