Hyperparathyroidism-Jaw Tumor Syndrome in Roma Families from Portugal Is Due to a Founder Mutation of the HRPT2 Gene

The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors and ossifying jaw fibromas. The gene causing HPT-JT, HRPT2, is located on chromosome 1q31.2 and consists of 17 exons that encode a 531-amino acid protein, designated parafibromin. We recently identified six Roma families in Portugal with 56 members (11 affected and 45 asymptomatic), who had the HPT-JT syndrome. We postulated that they may have a common ancestor and that the HPT-JT syndrome may be due to a mutation of the HRPT2 gene. Haplotype analysis using 14 chromosome 1q24-q32 polymorphic markers showed that the 11 affected individuals shared a common haplotype defined by seven markers that spanned an approximately 12.5-cM region, flanked centromerically by D1S202 and telomerically by D1S306. DNA sequence analysis identified a 2-bp (TG or GT) frameshift deletion in exon 8, which predicts a truncated parafibromin protein, in all 11 affected individuals. This mutatio...