Lessons from the Genetics of Laron Syndrome

Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: A preliminary report

“…In contradistinction, 24% of their first and seconddegree family members in the Israeli cohort and 12% of the relatives of patients from other countries reported malignancies. Laron syndrome is a rare recessive inherited disease found almost exclusively in populations from Mediterranean, Mid-Eastern, South Asia origin or their descendants [13][14][15]. Their total number is estimated to be around 200-300 [14], meaning that we have succeeded to survey half or more of the total number of patients.…”

Dimerization and Signal Transduction of the Growth Hormone Receptor

“…In general, Laron mutations either affect GH binding or result in GHR truncation mutants, which are unable to bind JAK2 (for review, see Ref. 28). However, GHR(D152H) is able to bind GH and contains an intact JAK2 binding region (26).…”

A half-century of studies of growth hormone insensitivity/Laron syndrome: A historical perspective

“…Subsequently, over 50 mutations of the GHR gene have been identified. In addition to the original exon 5, 6 deletion, another deletion of exon 5 has been described, along with numerous nonsense mutations, missense mutations, frameshift mutations, splice mutations, and a unique intronic mutation resulting in insertion of a pseudo-exon [25]. In 1997 a heterozygous dominant negative mutation of the intracellular domain of the GHR, resulting in a milder LS phenotype, was described in a British mother and daughter [26] and in 1998 a similar heterozygous point mutation also resulting in mild growth failure was described in Japanese siblings and their mother [27].…”