29 research outputs found
RET proto-oncogene in Sardinia: V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype
OBJECTIVE:
Genetic screening of RET proto-oncogene is a powerful tool for the early identification of familial cases of medullary thyroid carcinoma (MTC), comprising isolated familial thyroid medullary carcinoma (FMTC) and multiple endocrine neoplasia syndromes 2A (MEN-2A) and 2B (MEN-2B). We report the results obtained by RET mutation analysis of subjects living in Sardinia, an Italian island whose inhabitants display a peculiar genetic background due to geographic isolation and low immigration rate for several centuries.
DESIGN:
Retrospective study reporting data on 67 patients referred during the last 5 years for RET analysis because affected by MTC or first degree relatives of MTC patients.
MAIN OUTCOME:
Only three mutations were identified affecting codons 620 (exon 10), 634 (exon 11), and 804 (exon 14); surprisingly, the most prevalent mutation found was V804M (overall prevalence: 59%). This finding is quite different from previous studies carried out in other Caucasian and non-Caucasian populations, in which the frequency of the V804M mutation is consistently reported less than 5%. The phenotype associated to V804M mutation was mostly FMTC (16/17 cases = 94.1%), but in one case (5.9%) primary hyperparathyroidism was found, suggesting a MEN-2A.
CONCLUSIONS:
These results underline the importance of the genetic background in the distribution of RET mutations and should be taken into consideration when performing genetic evaluation of MTC patients
Studio della distribuzione del virus dell' epatite C (HCV) nella provincia di ORISTANO (SARDEGNA)mediante sequenziamento capillare
a novel germline mutation of men 1 gene in a patient with acromegaly and multiple endocrine tumors
A novel germline mutation of MEN 1 gene in a patient with acromegaly and multiple endocrine tumors
Germline mutations of the MEN 1 gene are responsible for multiple endocrine neoplasia type 1 (MEN 1), a dominantly inherited cancer syndrome characterized by tumors of the parathyroids, gastro-intestinal endocrine tissue, anterior pituitary and other endocrine tissues. We report on a 55-yr old woman, presentingwith active acromegaly (due to GH-secreting microadenoma), associated to bilateral adrenal
adenomatosis and Hürthle-cell thyroid neoplasia. No evidence of hyperparathyroidism or gastrinsecreting tumor was found. Peripheral blood genomic DNA was extracted, amplified by PCR, purified and analyzed by direct sequencing. The analysis revealed a heterozygous mutation in exon 4 of the MEN 1 gene: a G to A missense mutation at codon 229 (CGC→CAC), which changes arginine to histidine. This mutation causes loss of the HhaI restriction site and can thus be employed for a rapid familiar screening. This case represents a newly recognized germline mutation of the MEN 1 gene