Expanding the spectrum of clinical and genetic characteristics of distal arthrogryposis type 5 caused by heterozygous variants in the PIEZO2 gene

Abstract

Pathogenic heterozygous variants in the PIEZO2 gene cause distal arthrogryposis type 5 – a rare autosomal dominant disease, which is characterized by the development of congenital contractures, ophthalmoparesis, ptosis and restrictive respiratory disorders. We have presented clinical and genetic characteristics of seven Russian patients with distal arthrogryposis type 5 caused by previously described and newly identified nucleotide variants in the PIEZO2 gene. It was shown that the most severe clinical manifestations were found in patients with newly identified nucleotide variants c.8238G>A (p.Trp274Ter) and c.7095G>T (p.Trp2365Cys), while in patients with other previously described variants c.8181_8183delAGA (p.Glu2727del) and c.2134A>G (p.Met712Val) the clinical phenotype is more moderately expressed. The dynamics of phenotype formation were also noted. It has been shown that the disease progression may occur as the child grows and requires monitoring of this group of patients.