Diverse growth hormone receptor gene mutations in Laron syndrome

Journal Article · Sat May 01 04:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6220219

Berg, M A; Francke, U ^[1]; Gracia, R; Rosenbloom, A; Toledo, S P.A. ^[2]; Chernausek, S ^[3]; Guevara-Aguirre, J ^[4]; Hopp, M ^[5]; Rosenbloom, A; Argente, J ^[6]; Toledo, S P.A. ^[7]

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1. Stanford Univ. School of Medicine, CA (United States)
2. Univ. Autonoma, Madrid (Spain)
3. Children's Hospital Medical Center, Cincinnati, OH (United States)
4. Institute of Endocrinology, Metabolism, and Reproduction, Quito (Ecuador)
5. Univ. of Witwatersrand, Johannesburg (South Africa)
6. Univ. of Florida, Gainesville (United States)
7. Univ. of Sao Paulo (Brazil)

To better understand the molecular genetic basis and genetic epidemiology of Laron syndrome (growth-hormone insensitivity syndrome), the authors analysed the growth-hormone receptor (GHR) genes of seven unrelated affected individuals from the United States, South America, Europe, and Africa. They amplified all nine GHR gene exons and splice junctions from these individuals by PCR and screened the products for mutations by using denaturing gradient gel electrophoresis (DGGE). They identified a single GHR gene fragment with abnormal DGGE results for each affected individual, sequenced this fragment, and, in each case, identified a mutation likely to cause Laron syndrome, including two nonsense mutations (R43X and R217X), two splice-junction mutations, (189-1 G to T and 71+1 G to A), and two frameshift mutations (46 del TT and 230 del TA or AT). Only one of these mutations, R43X, has been previously reported. Using haplotype analysis, they determined that this mutation, which involves a CpG dinucleotide hot spot, likely arose as a separate event in this case, relative to the two prior reports of R43X. Aside from R43X, the mutations identified are unique to patients from particular geographic regions. Ten GHR gene mutations have now been described in this disorder. The authors conclude that Laron syndrome is caused by diverse GHR gene mutations, including deletions, RNA processing defects, translational stop codons, and missense codons. All the identified mutations involve the extracellular domain of the receptor, and most are unique to particular families or geographic areas. 35 refs., 3 figs., 1 tab.

• OSTI ID: 6220219
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:5; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
551000 -- Physiological Systems
59 BASIC BIOLOGICAL SCIENCES
AFRICA
ANIMAL GROWTH
DEVELOPED COUNTRIES
DISEASES
DNA HYBRIDIZATION
ELECTROPHORESIS
ENDOCRINE DISEASES
EPIDEMIOLOGY
EUROPE
GENE MUTATIONS
GROWTH
HEREDITARY DISEASES
HORMONES
HYBRIDIZATION
LATIN AMERICA
MEMBRANE PROTEINS
MUTATIONS
NORTH AMERICA
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
RECEPTORS
RNA PROCESSING
SOUTH AMERICA
STH
USA