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Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.
Clin Endocrinol (Oxf). 2005 Mar; 62(3):336-42.CE

Abstract

OBJECTIVE

To identify MEN1 gene mutations and characterize clinical manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1) in Taiwan.

PATIENTS AND METHODS

Eight unrelated subjects (one male and seven females, age range 26-70 years) with clinical manifestations of MEN1 were analysed. In addition, 45 relatives that included 10 affected (three males and seven females, age range 32-53 years) and 35 unaffected (17 males and 18 females, age range 15-80 years) subjects were evaluated. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis were performed according to standard procedures.

RESULTS

We identified heterozygous MEN1 gene mutations in all eight probands and 10 affected subjects as well as in 13 clinically asymptomatic relatives. Novel mutations included a missense mutation in a heterozygous mutation in exon 9 (GAC --> CAC) resulting in a substitution of aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon 556 of exon 10 (GAG --> TAG) resulting in a stop codon and termination (family 2); a missense mutation in exon 2 (GGG --> GAG) causing the substitution of glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion mutation in nucleotide 1200 of exon 8 resulting in frameshift and early termination (family 4). Affected subjects in families 5-7 shared the same C insertion at nucleotide 1650 of exon 10, similar to that previously described as a hotspot for mutation, and proband 8 had a previously described mutation in intron 4 of the MEN1 gene (IVS4-9 G --> A). We also found that 18 (58%) of our 31 MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical abnormalities without clinical symptoms, and nine (29%) were unaffected both clinically and biochemically.

CONCLUSIONS

We have identified four novel mutations in the MEN1 gene in patients with MEN1 in Taiwan.

Authors+Show Affiliations

Section of Biochemistry, Department of Pathology and Laboratory Medicine, Division of Metabolism and Endocrinology, Taipei Venterans General Hospital, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. tsjap@vghtpe.gov.twNo 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

15730416

Citation

Jap, Tjin-Shing, et al. "Novel Mutations in the MEN1 Gene in Subjects With Multiple Endocrine Neoplasia-1." Clinical Endocrinology, vol. 62, no. 3, 2005, pp. 336-42.
Jap TS, Chiu CY, Won JG, et al. Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1. Clin Endocrinol (Oxf). 2005;62(3):336-42.
Jap, T. S., Chiu, C. Y., Won, J. G., Wu, Y. C., & Chen, H. S. (2005). Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1. Clinical Endocrinology, 62(3), 336-42.
Jap TS, et al. Novel Mutations in the MEN1 Gene in Subjects With Multiple Endocrine Neoplasia-1. Clin Endocrinol (Oxf). 2005;62(3):336-42. PubMed PMID: 15730416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1. AU - Jap,Tjin-Shing, AU - Chiu,Chih-Yang, AU - Won,Justin Ging-Shing, AU - Wu,Yi-Chi, AU - Chen,Harn-Shen, PY - 2005/2/26/pubmed PY - 2005/6/17/medline PY - 2005/2/26/entrez SP - 336 EP - 42 JF - Clinical endocrinology JO - Clin Endocrinol (Oxf) VL - 62 IS - 3 N2 - OBJECTIVE: To identify MEN1 gene mutations and characterize clinical manifestations in Chinese kindred with multiple endocrine neoplasia type 1 (MEN1) in Taiwan. PATIENTS AND METHODS: Eight unrelated subjects (one male and seven females, age range 26-70 years) with clinical manifestations of MEN1 were analysed. In addition, 45 relatives that included 10 affected (three males and seven females, age range 32-53 years) and 35 unaffected (17 males and 18 females, age range 15-80 years) subjects were evaluated. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis were performed according to standard procedures. RESULTS: We identified heterozygous MEN1 gene mutations in all eight probands and 10 affected subjects as well as in 13 clinically asymptomatic relatives. Novel mutations included a missense mutation in a heterozygous mutation in exon 9 (GAC --> CAC) resulting in a substitution of aspartic acid by histidine at codon 418 (family 1); a nonsense mutation at codon 556 of exon 10 (GAG --> TAG) resulting in a stop codon and termination (family 2); a missense mutation in exon 2 (GGG --> GAG) causing the substitution of glycine by glutamic acid at codon 110 (family 3); and a deletion/insertion mutation in nucleotide 1200 of exon 8 resulting in frameshift and early termination (family 4). Affected subjects in families 5-7 shared the same C insertion at nucleotide 1650 of exon 10, similar to that previously described as a hotspot for mutation, and proband 8 had a previously described mutation in intron 4 of the MEN1 gene (IVS4-9 G --> A). We also found that 18 (58%) of our 31 MEN1 mutant carriers had clinical symptoms, whereas four (13%) had biochemical abnormalities without clinical symptoms, and nine (29%) were unaffected both clinically and biochemically. CONCLUSIONS: We have identified four novel mutations in the MEN1 gene in patients with MEN1 in Taiwan. SN - 0300-0664 UR - https://www.unboundmedicine.com/medline/citation/15730416/Novel_mutations_in_the_MEN1_gene_in_subjects_with_multiple_endocrine_neoplasia_1_ L2 - https://doi.org/10.1111/j.1365-2265.2005.02219.x DB - PRIME DP - Unbound Medicine ER -