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Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1).
Eur J Endocrinol. 1999 Nov; 141(5):475-80.EJ

Abstract

OBJECTIVE

Multiple endocrine neoplasia type 1 (MEN1) is a syndrome of endocrine tumors involving the parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned in 11q13. We aimed to assess the significance of MEN1 gene diagnostics in families with MEN1.

DESIGN

Sixteen probands of familial MEN1 and their 40 family members were subjected to the study.

METHODS

Full-length sequencing of the open reading frame and exon-intron boundaries in the MEN1 gene was performed with probands of familial MEN1. Family members were examined for the identified mutation in the proband.

RESULTS

We identified heterozygous germline mutations of the MEN1 gene in all of 16 Japanese MEN1 families examined, achieving the highest detectability of MEN1 mutations in familial MEN1 among studies that examined more than 10 families. Eleven kinds of the identified MEN1 germline mutations were novel. More than half were nonsense or frameshift mutations resulting in a premature stop codon (9/15; 60%), and no mutation hot spots or no apparent genotype-phenotype relationships were observed, in support of the results of other studies. We identified 40 mutant MEN1 gene carriers and 16 non-carriers in the course of the present study in those families.

CONCLUSIONS

Analysis of the germline mutations in the MEN1 gene, providing significantly useful clinical information to probands and family members of MEN1, should be considered as a standard procedure and categorized as belonging to Group 1 cancer predisposition testing by the American Society of Clinical Oncology.

Authors+Show Affiliations

Department of Laboratory Medicine, Kyoto University School of Medicine, Kyoto 606-8507, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10576763

Citation

Hai, N, et al. "Germline MEN1 Mutations in Sixteen Japanese Families With Multiple Endocrine Neoplasia Type 1 (MEN1)." European Journal of Endocrinology, vol. 141, no. 5, 1999, pp. 475-80.
Hai N, Aoki N, Matsuda A, et al. Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1). Eur J Endocrinol. 1999;141(5):475-80.
Hai, N., Aoki, N., Matsuda, A., Mori, T., & Kosugi, S. (1999). Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1). European Journal of Endocrinology, 141(5), 475-80.
Hai N, et al. Germline MEN1 Mutations in Sixteen Japanese Families With Multiple Endocrine Neoplasia Type 1 (MEN1). Eur J Endocrinol. 1999;141(5):475-80. PubMed PMID: 10576763.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1). AU - Hai,N, AU - Aoki,N, AU - Matsuda,A, AU - Mori,T, AU - Kosugi,S, PY - 1999/11/27/pubmed PY - 1999/11/27/medline PY - 1999/11/27/entrez SP - 475 EP - 80 JF - European journal of endocrinology JO - Eur J Endocrinol VL - 141 IS - 5 N2 - OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is a syndrome of endocrine tumors involving the parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned in 11q13. We aimed to assess the significance of MEN1 gene diagnostics in families with MEN1. DESIGN: Sixteen probands of familial MEN1 and their 40 family members were subjected to the study. METHODS: Full-length sequencing of the open reading frame and exon-intron boundaries in the MEN1 gene was performed with probands of familial MEN1. Family members were examined for the identified mutation in the proband. RESULTS: We identified heterozygous germline mutations of the MEN1 gene in all of 16 Japanese MEN1 families examined, achieving the highest detectability of MEN1 mutations in familial MEN1 among studies that examined more than 10 families. Eleven kinds of the identified MEN1 germline mutations were novel. More than half were nonsense or frameshift mutations resulting in a premature stop codon (9/15; 60%), and no mutation hot spots or no apparent genotype-phenotype relationships were observed, in support of the results of other studies. We identified 40 mutant MEN1 gene carriers and 16 non-carriers in the course of the present study in those families. CONCLUSIONS: Analysis of the germline mutations in the MEN1 gene, providing significantly useful clinical information to probands and family members of MEN1, should be considered as a standard procedure and categorized as belonging to Group 1 cancer predisposition testing by the American Society of Clinical Oncology. SN - 0804-4643 UR - https://www.unboundmedicine.com/medline/citation/10576763/Germline_MEN1_mutations_in_sixteen_Japanese_families_with_multiple_endocrine_neoplasia_type_1__MEN1__ L2 - https://eje.bioscientifica.com/doi/10.1530/eje.0.1410475 DB - PRIME DP - Unbound Medicine ER -