Germline mutations in the MEN1 gene: creation of a new splice acceptor site and insertion of 7 intron nucleotides into the mRNA.
The MEN1 tumor predisposition syndrome is caused by mutations in the MEN1 gene on human chromosome 11q13. We screened MEN1 gene exons 1-10 and flanking intron sequences from four different MEN1 families for mutations. In three families, heterozygous germline mutations within the exons were found, two of these representing novel mutations. In another family, all clinically affected members were heterozygous for a point mutation Gright curved arrow A within intron 4. Sequence analysis of cDNA from lymphocytes of the affected patients revealed that the intron mutation created a new acceptor splice site, leading to the inclusion of 7 bp of intronic sequence into the mRNA. The resulting frameshift generates a premature stop in codon 271. Intron borders should thus be screened for mutations in MEN1 diagnostics and cDNA sequence analysis is helpful in identifying pathophysiological consequences of intron mutations.
Engelbach
M
M
Department of Internal Medicine and Endocrinology, D-55131 Mainz, Germany.
Forst
T
T
Hankeln
T
T
Tratzky
M
M
Heerdt
S
S
Pfützner
A
A
Kann
P
P
Kunt
T
T
Schneider
S
S
Schmidt
E R
ER
Beyer
J
J
D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000302:isolation & purification; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000235:genetics*
D018076:DNA, Complementary; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger