TOR1A-associated arthrogryposis multiplex congenita 5 (AMC5, MIM: #618947) is a rare congenital disorder arising from bi-allelic variants in TOR1A. TOR1A encodes for Torsin-1A, a member of the AAA+ family of adenosine triphosphatases (ATPases) that localizes to the endoplasmic reticulum where it has been implicated in a variety of cellular functions, including protein folding, lipid metabolism, cytoskeletal organization and nuclear polarity. While heterozygous variant alleles in TOR1A cause classic early-onset torsion dystonia (DYT1 or DYT-TOR1A,7 MIM: #128100), patients with bi-allelic variants present with a distinct phenotype characterized by severe congenital arthrogryposis and a complex neurodevelopmental disorder (NDD).
TOR1A