Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma variant of MEN1 (MEN1Burin) in four kindreds from Newfoundland.
Familial multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with affected individuals developing parathyroid, gastrointestinal (GI) endocrine, and anterior pituitary tumors. Four large kindreds from the Burin peninsula/Fortune Bay area of Newfoundland with prominent features of prolactinomas, carcinoids, and parathyroid tumors (referred to as MEN1Burin) have been described, and they show linkage to 11q13, the same locus as that of MEN1. Haplotype analysis with 16 polymorphic markers now reveals that representative affected individuals from all four families share a common haplotype over a 2.5 Mb region. A nonsense mutation in the MEN1 gene has been found to be responsible for the disease in the affected members in all four of the MEN1Burin families, providing convincing evidence of a common founder.
Olufemi
S E
SE
Laboratory of Gene Transfer, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892-4442, USA.
Green
J S
JS
Manickam
P
P
Guru
S C
SC
Agarwal
S K
SK
Kester
M B
MB
Dong
Q
Q
Burns
A L
AL
Spiegel
A M
AM
Marx
S J
SJ
Collins
F S
FS
Chandrasekharappa
S C
SC
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D018703:Founder Effect; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D009523:Newfoundland and Labrador; D010375:Pedigree; D010911:Pituitary Neoplasms / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D015175:Prolactinoma / Q000235:genetics*
D005819:Genetic Markers; D004247:DNA