Growth hormone deficiency type IB caused by cryptic splicing of the GH-1 gene.
We have found a novel mutation in intron 4 of the GH-1 gene in a Bedouin kindred with isolated growth hormone deficiency type IB (IGHD IB). RFLP analysis suggested linkage between the GH-1 gene and IGHD. Nested PCR amplification followed by single stranded conformation polymorphism (SSCP) analysis indicated sequence variation between introns 2 and 4. Sequencing showed a G-->C transversion at the fifth base in the splice donor region of intron 4. Affected individuals were homozygous for the mutation, which creates a new Mae III restriction site. Reverse transcription and PCR of GH-1 transcripts in EBV transformed lymphocytes indicated predominance of a species lacking 73 bp of exon 4. Amplification with a bridging primer showed that the same mRNA species is present in lymphocytes from normal individuals. The first 102 amino acids of the predicted protein are identical to wild-type GH, but the next 94 amino acids are completely divergent.
Abdul-Latif
H
H
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Leiberman
E
E
Brown
M R
MR
Carmi
R
R
Parks
J S
JS
D017398:Alternative Splicing; D018912:Arabs; D001483:Base Sequence; D002675:Child, Preschool; D003241:Consanguinity; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007438:Introns; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D012333:RNA, Messenger; D019382:Human Growth Hormone