Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene.

Date publication

janvier 2024

Journal

Clinical genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr HUET Frédéric , Pr FAIVRE Laurence , Pr PHILIPPE Christophe , Dr NAMBOT Sophie , Mr DUFFOURD Yannis , Pr THAUVIN-ROBINET Christel

Tous les auteurs :
Malbos M, Wakeling E, Gautier T, Boespflug-Tanguy O, Busby L, Taylor-Miller T, Dudoignon B, Bokov P, Govin J, Grisval M, Rega A, Mourot De Rougemont MG, Aubriot-Lorton MH, Darmency V, Bensignor C, Houzel A, Huet F, Denommé-Pichon AS, Delanne J, Tran Mau-Them F, Bruel AL, Safraou H, Nambot S, Garde A, Philippe C, Duffourd Y, Vitobello A, Faivre L, Thauvin-Robinet C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/38287449

Résumé

Achaete-Scute Family basic-helix-loop-helix (bHLH) Transcription Factor 1 (ASCL1) is a proneural transcription factor involved in neuron development in the central and peripheral nervous system. While initially suspected to contribute to congenital central hypoventilation syndrome-1 (CCHS) with or without Hirschsprung disease (HSCR) in three individuals, its implication was ruled out by the presence, in one of the individuals, of a Paired-like homeobox 2B (PHOX2B) heterozygous polyalanine expansion variant, known to cause CCHS. We report two additional unrelated individuals sharing the same sporadic ASCL1 p.(Glu127Lys) missense variant in the bHLH domain and a common phenotype with short-segment HSCR, signs of dysautonomia, and developmental delay. One has also mild CCHS without polyalanine expansion in PHOX2B, compatible with the diagnosis of Haddad syndrome. Furthermore, missense variants with homologous position in the same bHLH domain in other genes are known to cause human diseases. The description of additional individuals carrying the same variant and similar phenotype, as well as targeted functional studies, would be interesting to further evaluate the role of ASCL1 in neurocristopathies.

Mots clés

ASCL1, Dysautonomia, Haddad syndrome, Hirschsprung disease, basic-helix-loop-helix domain, congenital central hypoventilation syndrome-1, neurocristopathies

Référence

Clin Genet. 2024 01 29;: