Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome)

L. Baumbach, Adam Schiavi, R. Bartlett, E. Perera, J. Day, M. R. Brown, S. Stein, M. Eidson, J. S. Parks, W. Cleveland

Research output: Contribution to journalArticle

Abstract

We have characterized the GH receptor mutation that is responsible for extreme short stature and GH insensitivity in a Bahamian genetic isolate. Heights of affected individuals ranged from -4.0 to 6.3 SD. Like others with Laron's syndrome, they had normal to high serum GH concentrations and low serum insulin-like growth factor 1 concentrations. Circulating levels of GH- binding protein activity were below limits of detection. Amplification of exons 2-7 and screening with single strand conformational polymorphism analysis located an abnormality in exon 7. Sequencing identified homozygosity for a C to T transition in the third position of codon 236. Reverse transcription and PCR amplification of complementary DNA from lymphocytes showed that this same sense mutation generated a new splice donor site 63 bp 5' to the normal exon 7 splice site. This novel site was used to the exclusion of the normal site in homozygotes. Both normal and variant messenger ribonucleic acid species were detected in heterozygotes. The predicted protein lacks 21 amino acids, including those defining the WS-like motif of the GH receptor extracellular domain. The high frequency of Laron's syndrome in this isolated island population probably reflects the introduction of the G236 splice mutation by a settler early in the 300-yr history of English settlement.

Original languageEnglish (US)
Pages (from-to)444-451
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Laron Syndrome
Growth Hormone
Exons
Mutation
Amplification
RNA Splice Sites
Lymphocytes
Homozygote
Somatomedins
Transcription
Heterozygote
Polymorphism
Serum
Islands
Codon
Reverse Transcription
Limit of Detection
Screening
Complementary DNA
RNA

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome). / Baumbach, L.; Schiavi, Adam; Bartlett, R.; Perera, E.; Day, J.; Brown, M. R.; Stein, S.; Eidson, M.; Parks, J. S.; Cleveland, W.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 82, No. 2, 1997, p. 444-451.

Research output: Contribution to journalArticle

Baumbach, L. ; Schiavi, Adam ; Bartlett, R. ; Perera, E. ; Day, J. ; Brown, M. R. ; Stein, S. ; Eidson, M. ; Parks, J. S. ; Cleveland, W. / Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome). In: Journal of Clinical Endocrinology and Metabolism. 1997 ; Vol. 82, No. 2. pp. 444-451.
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