Two novel mutations in the MEN1 gene in subjects with multiple endocrine neoplasia-1.
Multiple endocrine neoplasia type 1 (MEN1) is characterized by parathyroid, enteropancreatic endocrine and pituitary adenomas as well as germline mutation of the MEN1 gene. We describe 2 families with MEN1 with novel mutations in the MEN1 gene. One family was of Turkish origin, and the index patient had primary hyperparathyroidism (PHPT) plus a prolactinoma; three relatives had PHPT only. The index patient in the second family was a 46-yr-old woman of Chinese origin living in Taiwan. This patient presented with a complaint of epigastric pain and watery diarrhea over the past 3 months, and had undergone subtotal parathyroidectomy and enucleation of pancreatic islet cell tumor about 10 yr before. There was also a prolactinoma. Sequence analysis of the MEN1 gene from leukocyte genomic DNA revealed heterozygous mutations in both probands. The Turkish patient and her affected relatives all had a heterozygous A to G transition at codon 557 (AAG-->GAG) of exon 10 of MEN1 that results in a replacement of lysine by glutamic acid. The Chinese index patient and one of her siblings had a heterozygous mutation at codon 418 of exon 9 (GAC-->TAT) that results in a substitution of aspartic acid by tyrosine. In conclusion, we have identified 2 novel missense mutations in the MEN1 gene.
Ozturk
M
M
Department of Endocrinology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey.
Chiu
C Y
CY
Akdeniz
N
N
Jenq
S F
SF
Chang
S C
SC
Hsa
C Y
CY
Jap
T S
TS
D000236:Adenoma / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D020125:Mutation, Missense; D010282:Parathyroid Neoplasms / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics; D015175:Prolactinoma / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013624:Taiwan; D014421:Turkey
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins