PMID- 10664521
OWN - NLM
STAT- MEDLINE
DCOM- 20000331
LR  - 20221207
IS  - 0804-4643 (Print)
IS  - 0804-4643 (Linking)
VI  - 142
IP  - 2
DP  - 2000 Feb
TI  - A novel mutation of the MEN1 gene in a Japanese kindred with familial isolated 
      primary hyperparathyroidism.
PG  - 138-43
AB  - OBJECTIVE: To determine whether familial isolated hyperparathyroidism (FIHP) is a 
      variant of multiple endocrine neoplasia type 1 (MEN1) we analyzed the MEN1 gene 
      in such a kindred. DESIGN AND METHODS: The study included the 70-year-old proband 
      and nine relatives. Blood was drawn for biochemical evaluation and germline 
      mutation analysis by direct sequencing of the MEN1 gene amplified by PCR. A 
      hyperplastic parathyroid gland obtained from a family member served for a loss of 
      heterozygosity (LOH) study. RESULTS: Three members from two generations in this 
      kindred were found to have primary hyperparathyroidism, while none had clinical 
      or biochemical evidence of MEN1, MEN2 or hyperparathyroidism--jaw tumor syndrome. 
      Analysis of germline DNA in the proband showed a missense mutation (GGC-->GAC) at 
      codon 305 in exon 7 of the MEN1 gene that predicts an amino acid change from 
      glycine to aspartic acid (G305D). This mutation segregated with primary 
      hyperparathyroidism in the kindred, and, in addition, there were two asymptomatic 
      mutant-gene carriers at relatively advanced ages. In contrast, the mutation was 
      not detected in genomic DNA from five unaffected individuals and from 50 healthy 
      subjects. The LOH study showed a loss of the wild-type allele, which confirmed 
      that a functional defect of the MEN1 gene product, menin, is etiological for 
      FIHP. CONCLUSIONS: FIHP is a genetically heterogeneous disease with a subset 
      linked to MEN1, most likely representing a variant of MEN1. The late onset and 
      the reduced penetrance of disease found in this kindred may be related to the 
      site and the type of mutation, although the precise mechanism involved is unknown 
      at present.
FAU - Honda, M
AU  - Honda M
AD  - Fourth Department of Medicine, Teikyo University School of Medicine, Kawasaki, 
      Kanagawa, Japan.
FAU - Tsukada, T
AU  - Tsukada T
FAU - Tanaka, H
AU  - Tanaka H
FAU - Maruyama, K
AU  - Maruyama K
FAU - Yamaguchi, K
AU  - Yamaguchi K
FAU - Obara, T
AU  - Obara T
FAU - Yamaji, T
AU  - Yamaji T
FAU - Ishibashi, M
AU  - Ishibashi M
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Radiopharmaceuticals)
RN  - 971Z4W1S09 (Technetium Tc 99m Sestamibi)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Asian People
MH  - Base Sequence/genetics
MH  - Female
MH  - *Germ-Line Mutation/genetics
MH  - Heterozygote
MH  - Humans
MH  - Hyperparathyroidism/diagnostic imaging/*genetics
MH  - Japan
MH  - Loss of Heterozygosity
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Mutation, Missense
MH  - Pedigree
MH  - Radionuclide Imaging
MH  - Radiopharmaceuticals
MH  - Technetium Tc 99m Sestamibi
EDAT- 2000/02/09 00:00
MHDA- 2000/02/09 00:01
CRDT- 2000/02/09 00:00
PHST- 2000/02/09 00:00 [pubmed]
PHST- 2000/02/09 00:01 [medline]
PHST- 2000/02/09 00:00 [entrez]
AID - 1420138 [pii]
AID - 10.1530/eje.0.1420138 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2000 Feb;142(2):138-43. doi: 10.1530/eje.0.1420138.