The origin of the p.E180 growth hormone receptor gene mutation

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Laron syndrome, an autosomal recessive condition of extreme short stature, is caused by the absence or dysfunction of the growth hormone receptor. A recurrent mutation in the GHR gene, p.E180, did not alter the encoded amino acid, but activated a cryptic splice acceptor resulting in a receptor protein with an 8-amino acid deletion in the extracellular domain. This mutation has been observed among Sephardic Jews and among individuals in Ecuador, Brazil and Chile, most notably in a large genetic isolate in Loja, Ecuador. A common origin has been postulated based on a shared genetic background of markers flanking this mutation, suggesting that the Lojanos (and others) may have Sephardic (Converso) Jewish ancestry. Analysis of the population structure of Lojanos based on genome-wide analysis demonstrated European, Sephardic Jewish and Native American ancestry in this group. X-autosomal comparison and monoallelic Y chromosomal and mitochondrial genetic analysis demonstrated gender-biased admixture between Native American women and European and Sephardic Jewish men. These findings are compatible with the co-occurrence of the Inquisition and the colonization of the Americas, including Converso Jews escaping the Inquisition in the Iberian Peninsula. Although not found among Lojanos, Converso Jews also brought founder mutations to contemporary Hispanic and Latino populations in the BRCA1 (c.68_69delAG) and BLM (c.2207_2212delATCTGAinsTAGATTC) genes.

Original languageEnglish (US)
JournalGrowth Hormone and IGF Research
DOIs
StateAccepted/In press - Jun 4 2015

Fingerprint

Somatotropin Receptors
Jews
Ecuador
Mutation
North American Indians
Hispanic Americans
Genes
Laron Syndrome
Amino Acids
Chile
Genetic Markers
Population
Brazil
Genome
Proteins

Keywords

  • Founder mutation
  • GHR deficiency
  • GHR gene
  • Laron syndrome
  • Population genetics

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The origin of the p.E180 growth hormone receptor gene mutation. / Ostrer, Harry.

In: Growth Hormone and IGF Research, 04.06.2015.

Research output: Contribution to journalArticle

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