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

• Type: Article in International Scientific Journal
• Date: 2004

Authors

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

Journal

Title: Journal of Clinical Endocrinology and Metabolism

Vol. 89

Pages: 1747-1752

ISSN: 0021-972X

Publisher: Endocrine Society

Indexing

ISI Web of Knowledge - 59 Citations

Scopus - 63 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6