Hyperparathyroidism-jaw tumor syndrome in Roma families from Portugal is due to a founder mutation of the HRPT2 gene
| Autor: | Davide Carvalho, Laura Guerra, Amélia Oliveira, Brian Harding, Valeriano Leite, Luís G. Sobrinho, Rajesh V. Thakker, B M Cavaco, Maria-Amparo Santos, K J Bradley |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty Aging Endocrinology Diabetes and Metabolism Clinical Biochemistry Parafibromin Penetrance Biology medicine.disease_cause Biochemistry Frameshift mutation Exon Endocrinology Internal medicine medicine Humans Aged Genetics Mutation Sex Characteristics Portugal Hyperparathyroidism Tumor Suppressor Proteins Biochemistry (medical) Haplotype Proteins DNA Syndrome Middle Aged Jaw Neoplasms Hyperparathyroidism-Jaw Tumor Syndrome Founder Effect Pedigree Haplotypes Female Founder effect |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 89(4) |
| ISSN: | 0021-972X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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