Disease-causing variants identified in four genes underlying arthrogryposis-associated syndromes

Arthrogryposis is a rare inherited condition characterized by multiple joint contractures that limit the movement in one or more joints, leading to decreased flexibility. This condition can affect joints across the body including elbows, shoulders, wrists, knees, hips, and fingers. This study describes four different families having hallmark features of arthrogryposis. The whole-exome sequencing followed by Sanger sequencing was performed for all the families using standard methods. Whole-exome sequencing revealed three novel variants and one already reported variant in four different genes. In family A, we identified an already reported homozygous variant (c.834delG; p.Ser279Alafs*191) in exon 8 of the LGI4 gene (NM_139284.3). Family B revealed a potentially causative novel homozygous variant (c.2102C>T; p.Pro701Leu) in exon 16 of the ECEL1 gene (NM_004826.4), whereas in family C we identified a novel homozygous variant (c.4244_4245del; p.Thr1415Serfs*10) in exon 7 of the PIEZO2 gene (NM_001378183.1), and an already reported homozygous deletion (exons 1–10 deletion) in the CNTNAP1 gene (NM_003632.3) was identified in family D. Our results confirm the involvement of these genes in the formation of multisystemic contractures in humans and extend the mutation and clinical spectrum of four distinct forms of arthrogryposis.