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, presenting with active acromegaly (due to GH-secreting microadenoma), associated to bilateral adrenal adenomatosis and Hürthle-cell thyroid neoplasia. No evidence of hyperparathyroidism or gastrin-secreting 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 Hhal 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.
Pinna
G
G
University of Cagliari, Cagliari, Italy.
Orgiana
G
G
Carcassi
C
C
Alba
F
F
Cetani
F
F
Pardi
E
E
Marcocci
C
C
Mariotti
S
S
D000172:Acromegaly / Q000235:genetics*; D000236:Adenoma / Q000235:genetics; D000310:Adrenal Gland Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins
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