Biallelic <i>CRELD1</i> variants cause severe muscle weakness and infantile epilepsy.

ABSTRACT: Nicotinic acetylcholine receptors are widely expressed in the peripheral and central nervous systems. Mutations in acetylcholine receptor-subunit genes have been associated with neuromuscular diseases, such as arthrogryposis multiplex congenita (AMC) and epilepsy. We report a patient with arthrogryposis, severe muscle weakness and neurodevelopmental delay. During his first year of life, he developed therapy-refractory epilepsy. Using whole-exome sequencing, we identified the compound pathogenic variants c. 875G>A (p. Cys292Tyr) and c. 959delA (p. Gln320Argfs*25) in the cysteine-rich with epidermal growth factor-like domain protein 1 gene (CRELD1, NM_001077415.3). Recently, functional studies have shown that CRELD1 is a membrane-associated endoplasmic reticulum-resident protein disul

SUBMITTER: D'Alessandro M 

PROVIDER: S-EPMC12448699 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature