Novel biallelic COL25A1 variants broaden the clinical spectrum from congenital cranial dysinnervation disorders to fetal lethal phenotypes.

ABSTRACT: Biallelic variants in COL25A1 have been associated with isolated congenital cranial dysinnervation disorders (CCDDs) and arthrogryposis multiplex congenital (AMC) with or without CCDD. COL25A1 encodes collagen XXV that belongs to the subfamily of membrane-associated collagens with interrupted triple helices. COL25A1 contains four non-collagenous and three collagenous domains. Three alternatively spliced COL25A1 transcript variants are known. In mice, Col25a1 is required for intramuscular motor innervation and cranial motor neuron development. We report seven subjects with novel biallelic COL25A1 pathogenic variants, including three AMC-affected individuals, one of whom died in infancy, and four unrelated fetuses. We expand the associated phenotypic spectrum as fetuses showed lethal phenoty

SUBMITTER: Harms FL 

PROVIDER: S-EPMC12669723 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature