495 Mutations in different domains of bullous pemphigoid antigen-1 (BPGA1) encoded by DST result in either epidermolysis bullosa simplex or musculoskeletal and neuronal deformities-associated HSAN-VI

DST encodes bullous pemphigoid antigen-1 (BPAG1), a protein with eight tissue-specific isoforms expressed in the skin, muscle, brain, and nerves. Accordingly, mutations this gene cause different phenotypes, including epidermolysis bullosa simplex (EBS) hereditary sensory autonomic neuropathy type VI (HSAN-VI). The genotype-phenotype correlation is attested to by 19 distinct but not well established for both disorders. In study, we performed next-generation sequencing (NGS) on two families phenotypic presentations, one fetus (P1) musculoskeletal neurological malformations prenatal ultrasound family history, 15-year-old female (P2) skin blistering. P1 had novel homozygous nonsense mutation, DST: NM_001144769, c.3805C>T, p.R1269* within region of homozygosity (ROH). This plakin domain, ablates all BPGA1 leading extracutaneous phenotypes P1. P2 has recurrent mutation NM_001723.7, c.3370C>T, p.Gln1124* that presented giant, trauma-induced blisters without involvement. located coiled-coil domain present isoform DST, BPGA1-e, associated EBS. summary, report Iranian variants, expanding genotypic spectrum DST.