Molecular defects of the growth hormone receptor gene, including a new mutation, in Laron syndrome patients in Israel: relationship between defects and ethnic groups.
BACKGROUND
Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH receptor gene.


OBJECTIVE
To characterize the molecular defects of the GH-R in Laron syndrome patients followed in our clinic.


METHODS
Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.


RESULTS
Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.


CONCLUSIONS
This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.
Shevah
Orit
O
Endocrinology and Diabetes Research Unit, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.
Rubinstein
Menachem
M
Laron
Zvi
Z
D000328:Adult; D002648:Child; D015331:Cohort Studies; D003241:Consanguinity; D004392:Dwarfism / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007557:Israel / Q000453:epidemiology; D009154:Mutation; D011110:Polymorphism, Genetic; D011986:Receptors, Somatotropin / Q000235:genetics*; D017422:Sequence Analysis, DNA
D011986:Receptors, Somatotropin