A Novel Splice Variant in ERGIC1 Causes Arthrogryposis Multiplex Congenita—Characterization Using Urine‐Derived Cells

Arthrogryposis multiplex congenita (AMC) is defined as the presence of joint contractures affecting at least two body regions at birth. Three different ERGIC1 variants have been reported in individuals with AMC. Here, we report on a 16‐year‐old male with a homozygous ERGIC1 c.250+1G>A variant that was classified as a variant of uncertain significance on trio genome analysis. The proband's phenotype resembled that of previously reported individuals with ERGIC1 variants, but also included an absent patella and advanced bone age, which have not been reported in ERGIC1 ‐related AMC. RNA extracted from urine‐derived cells showed a splice defect of exon 4. This caused a deletion of two base pairs from the end of the exon, expected to result in a frameshift and nonsense‐mediated decay. This report expands the number of ERGIC1 variants linked to AMC and demonstrates the utility of RNA‐based diagnostic methods.