SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.

ABSTRACT: Upregulated signal flow through RAS and the mitogen-associated protein kinase (MAPK) cascade is the unifying mechanistic theme of the RASopathies, a family of disorders affecting development and growth. Pathogenic variants in more than 20 genes have been causally linked to RASopathies, the majority having a dominant role in promoting enhanced signaling. Here, we report that SPRED2 loss of function is causally linked to a recessive phenotype evocative of Noonan syndrome. Homozygosity for three different variants-c.187C>T (p.Arg63^∗), c.299T>C (p.Leu100Pro), and c.1142_1143delTT (p.Leu381Hisfs^∗95)-were identified in four subjects from three families. All variants severely affected protein stability, causing accelerated degradation, and variably perturbed SPRED2 functiona

SUBMITTER: Motta M 

PROVIDER: S-EPMC8595899 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature