Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene

• Tipo: Artigo em Revista Científica Internacional
• Data: 2004

Autores

Cavaco, BM (Autor) Outra; Guerra, L (Autor) Outra; Bradley, KJ (Autor) Outra; Carvalho, Davide (Autor) FMUP; Harding, B (Autor) Outra; Oliveira, A (Autor) Outra; Santos, MA (Autor) Outra; Sobrinho, LG (Autor) Outra; Thakker, RV (Autor) Outra; Leite, V (Autor) Outra

Revista

Título: Journal of Clinical Endocrinology and Metabolism

Vol. 89

Páginas: 1747-1752

ISSN: 0021-972X

Editora: Endocrine Society

Indexação

ISI Web of Knowledge - 59 Citações

Scopus - 63 Citações

Outras Informações

ID Authenticus: P-000-B0Z

DOI: 10.1210/jc.2003-031016

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6