Abstract
UNC50 encodes a transmembrane protein that plays a crucial role in L-acetylcholine receptor trafficking and thus cholinergic transmission at the neuromuscular junction. Previously, a biallelic loss-of-function variant in UNC50 was reported in an individual with lethal arthrogryposis multiplex congenita. We herein describe affected individuals from two unrelated families with arthrogryposis multiplex congenita in one family and a severe early-onset neuromuscular dysfunction in the other, both within the spectrum of congenital myasthenia syndrome. A biallelic variant, c.644-13_644-9del, p.? in intron 5 of UNC50 (NM_014044.7) was identified in both families. Transcript analysis in the peripheral blood cDNA of the heterozygous carrier parents of family 1 revealed that the c.644-13_644-9del variant leads to aberrant splicing. With these findings, we validated the association of disease-causing variants in UNC50 with congenital myasthenia syndrome.