A Newly Recognized Germline Mutation of MEN1 Gene Identified in a Patient with Parathyroid Adenoma and Carcinoma

Kuma Hospital, Kōbe, Hyōgo, Japan
Endocrine (Impact Factor: 3.88). 04/2012; 12(3):223-226. DOI: 10.1385/ENDO:12:3:223


We report on a patient with primary hyperparathyroidism, owing to the concurrence of parathyroid adenoma with carcinoma, who
had a newly recognized germline mutation of the multiple endocrine neoplasia type 1 gene (MEN1 gene). The patient underwent total parathyroidectomy, and histological examination revealed parathyroid carcinoma and multiple
adenoma of the other three glands. Genetic analysis revealed a newly recognized heterozygous germline mutation (842deIC, exon
4) of the MEN1 gene. Both imaging studies and laboratory data showed no evidence of MEN 1 in the patient. Four family members—three sisters
and one daughter—had neither clinical features of MEN 1 nor genetic evidence of the MEN1 gene. This is the first report of a germline mutation of the MEN 1 gene found in a patient who exhibited the concurrence of parathyroid adenoma with carcinoma, suggesting that long-term hyperactivity
of the parathyroids may result in the formation of carcinoma.

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    ABSTRACT: Heterozygous germline mutations of the tumor suppressor gene MEN1 are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited familial cancer syndrome characterized by the combined occurrence of pituitary, parathyroid, and enteropancreatic tumors. Various types of mutations likely causing loss of the gene function have been identified throughout the entire gene region in patients with MEN1 and related disorders including a small fraction of familial isolated hyperparathyroidism (FIHP). Neither mutation hot spot nor phenotype-genotype correlation has been established in classical MEN1, although some missense mutations may be specifically associated with a phenotype of FIHP. Familial isolated pituitary tumor and atypical familial MEN1 consisting of only pituitary tumor and hyperparathyroidism usually lack germline MEN1 mutations, suggesting that these familial endocrine tumor syndromes are genetic entities distinct from MEN1. DNA test for MEN1 germline mutations is a robust tool for diagnosis of predisposition to MEN1, and will be useful for the counseling and management of patients and their families. In this review, we will summarize the most recent findings on the MEN1 gene, focusing primarily on germline mutations and associated diseases.
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