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Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism

Carling, T ; Correa, Pamela ; Hessman, O ; Hedberg, J ; Skogseid, B ; Lindberg, D LU ; Rastad, J ; Westin, G and Akerström, G (1998) In The Journal of clinical endocrinology and metabolism 83(8). p.2960-2963
Abstract

Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously... (More)

Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.

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author
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publishing date
type
Contribution to journal
publication status
published
keywords
Adenoma/genetics, Aged, Aged, 80 and over, Chromosomes, Human, Pair 11, Female, Frameshift Mutation, Gene Deletion, Humans, Hyperparathyroidism/genetics, Loss of Heterozygosity, Male, Microsatellite Repeats, Middle Aged, Multiple Endocrine Neoplasia Type 1/genetics, Mutation, Parathyroid Hormone/blood, Parathyroid Neoplasms/genetics
in
The Journal of clinical endocrinology and metabolism
volume
83
issue
8
pages
2960 - 2963
publisher
Oxford University Press
external identifiers
  • pmid:9709976
  • scopus:0031759392
ISSN
0021-972X
DOI
10.1210/jcem.83.8.4977
language
English
LU publication?
no
id
5263108a-5039-43be-ad27-b25253c3d1ee
date added to LUP
2021-12-29 11:37:55
date last changed
2024-03-09 01:18:55
@article{5263108a-5039-43be-ad27-b25253c3d1ee,
  abstract     = {{<p>Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.</p>}},
  author       = {{Carling, T and Correa, Pamela and Hessman, O and Hedberg, J and Skogseid, B and Lindberg, D and Rastad, J and Westin, G and Akerström, G}},
  issn         = {{0021-972X}},
  keywords     = {{Adenoma/genetics; Aged; Aged, 80 and over; Chromosomes, Human, Pair 11; Female; Frameshift Mutation; Gene Deletion; Humans; Hyperparathyroidism/genetics; Loss of Heterozygosity; Male; Microsatellite Repeats; Middle Aged; Multiple Endocrine Neoplasia Type 1/genetics; Mutation; Parathyroid Hormone/blood; Parathyroid Neoplasms/genetics}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{2960--2963}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of clinical endocrinology and metabolism}},
  title        = {{Parathyroid MEN1 gene mutations in relation to clinical characteristics of nonfamilial primary hyperparathyroidism}},
  url          = {{http://dx.doi.org/10.1210/jcem.83.8.4977}},
  doi          = {{10.1210/jcem.83.8.4977}},
  volume       = {{83}},
  year         = {{1998}},
}