SCYL2-related autosomal recessive neurodevelopmental disorders: Arthrogryposis multiplex congenita-4 and beyond?
Fiche publication
Date publication
août 2024
Journal
Clinical genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence, Pr PHILIPPE Christophe, Mr DUFFOURD Yannis, Pr THAUVIN-ROBINET Christel
Tous les auteurs :
Malbos M, Vera G, Sheth H, Schnur RE, Juven A, Brehin AC, Sheth J, Gandhi A, Shapiro FL, Bruel AL, Marguet F, Begtrup A, Monaghan KG, Safraou H, Brasseur-Daudruy M, Mau-Them FT, Duffourd Y, Faivre L, Thauvin-Robinet C, Benke PJ, Philippe C
Lien Pubmed
Résumé
SCY1-like protein 2 (SCYL2) is a member of the SCY1-like pseudokinase family which regulates secretory protein trafficking. It plays a crucial role in the nervous system by suppressing excitotoxicity in the developing brain. Scyl2 knockout mice have excess prenatal mortality and survivors show severe neurological dysfunction. Bi-allelic loss-of-function (LOF) variants in SCYL2 were recently associated with arthrogryposis multiplex congenita-4 (AMC4) following the report of 6 individuals from two consanguineous unrelated families. The AMC4 phenotype described included severe arthrogryposis, corpus callosum agenesis, epilepsy and frequently, early death. We describe here two additional similarly affected individuals with AMC4, including one diagnosed in the prenatal period, with bi-allelic LOF variants in SCYL2, and two individuals homozygous for missense variants in the protein kinase domain of SCYL2 and presenting with developmental delay only. Our study confirms the association of SCYL2 with AMC4 and suggests a milder phenotype can occur, extending the phenotypic spectrum of autosomal recessive SCYL2-related disorders.
Mots clés
SCYL2, arthrogryposis, arthrogryposis multiplex congenital‐4, loss‐of‐function, missense
Référence
Clin Genet. 2024 08 21;: