Identification of a splice-site mutation in the human growth hormone-variant gene.
The human growth-hormone-variant (hGH-V) gene normally expresses two alternatively spliced forms of mRNA--hGH-V and hGH-V2--in the placenta. hGH-V2 mRNA differs from hGH-V rDNA by the retention of intron 4 and represents approximately 15% of transcripts at term. In a survey of hGH-V gene expression in 20 placentas of gestational age 8-40 wk, we detected a single placenta that contained, in addition to the two normal hGH-V mRNA species, a set of two slightly larger hGH-V mRNAs. Sequence analysis of the elongated hGH-V mRNA demonstrated retention of the first 12 bases of intron 2, resulting from both a base substitution at the intron 2 splice-donor dinucleotide (GT----AT) and activation of a cryptic splice-donor site 12 bases downstream. Survey of a total of 60 additional chromosomes failed to reveal additional incidence of this mutation. The mutation, which we have designated hGH-Vintron 2, pos 1 (G----A), represents both an initial example of a nondeletional mutation within the hGH-V gene and corresponding structural alteration in the encoded hGH-V hormone.
MacLeod
J N
JN
Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144.
Liebhaber
S A
SA
MacGillivray
M H
MH
Cooke
N E
NE
D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D014644:Genetic Variation; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010920:Placenta / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013006:Growth Hormone