title: Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene.
abstract: 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 mutation was also found in 19 unaffected individuals (age range, 12-74 yr) who shared the affected haplotype, suggesting a low age-related penetrance for HPT-JT in these families. Thus, the HPT-JT syndrome in six Roma families from Portugal is due to a novel founder mutation in the HRPT2 gene.
authors.affiliation: Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Francisco Gentil, Centro Regional de Oncologia de Lisboa, Sociedade Anónima, 1099-023 Lisboa, Portugal.
authors.forename: Branca M
authors.initials: BM
authors.lastname: Cavaco
authors.forename: Laura
authors.initials: L
authors.lastname: Guerra
authors.forename: Karin J
authors.initials: KJ
authors.lastname: Bradley
authors.forename: Davide
authors.initials: D
authors.lastname: Carvalho
authors.forename: Brian
authors.initials: B
authors.lastname: Harding
authors.forename: Amélia
authors.initials: A
authors.lastname: Oliveira
authors.forename: Maria-Amparo
authors.initials: MA
authors.lastname: Santos
authors.forename: Luís G
authors.initials: LG
authors.lastname: Sobrinho
authors.forename: Rajesh V
authors.initials: RV
authors.lastname: Thakker
authors.forename: Valeriano
authors.initials: V
authors.lastname: Leite
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D004247:DNA / Q000235:genetics; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D007573:Jaw Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D011174:Portugal; D011506:Proteins / Q000235:genetics*; D012727:Sex Characteristics; D013577:Syndrome; D025521:Tumor Suppressor Proteins
chemical_list: C454900:CDC73 protein, human; D011506:Proteins; D025521:Tumor Suppressor Proteins; D004247:DNA