Haplotype analysis of the growth hormone releasing hormone receptor locus in three apparently unrelated kindreds from the indian subcontinent with the identical mutation in the GHRH receptor

Abstract

The growth hormone releasing hormone receptor (GHRHR) plays a critical role in growth. We identified three nominally unrelated kindreds harboring the identical mutation (E72X) in GHRHR, the gene that encodes GHRHR; all three families originated in the Indian subcontinent. Because of the relative geographic proximity of these populations, we employed haplotype analysis in the region of GHRHR to determine the likelihood that this mutation occurred in a common ancestor rather than having occurred on separate occasions in different individuals. Members of all three kindreds segregating the E72X mutation were genotyped for highly polymorphic dinucleotide repeat microsatellites in a 15.5 centimorgan (cM) region around GHRHR on chromosome 7p15. We conclude that the affected individuals share a common ancestor, and we use the association with linked markers to estimate the age of this unique mutation.

A nonsense mutation (E72X) in growth hormone releasing hormone receptor (GHRHR) gene is the major cause of familial isolated growth hormone deficiency in Western region of India: founder effect suggested by analysis of dinucleotide repeat polymorphism close to GHRHR gene

“…Very recently, Wajnrajch et al [13] reported haplotype analysis of the GHRHR locus in three unrelated kindreds with E72X mutation from the Indian subcontinent reported previously [3][4][5]. Haplotyping for nine highly polymorphic dinucleotide repeat microsatellites in a 15.5 centimorgan region around GHRHR locus revealed a high degree of similarity and identity in the haplotypes on chromosome 7 among the three kindred [13], supporting our hypothesis.…”

“…Haplotyping for nine highly polymorphic dinucleotide repeat microsatellites in a 15.5 centimorgan region around GHRHR locus revealed a high degree of similarity and identity in the haplotypes on chromosome 7 among the three kindred [13], supporting our hypothesis. Indeed, the locus closest to GHRHR gene analyzed by Wajnrajch et al (D7SMW2) appears identical to 13 kb downstream locus in the present report.…”

“…The mutation of GHRHR gene (E72X) detected in this study is identical to the mutation previously described [3][4][5]13]. Other mutations in GHRHR gene have been reported in patients with recessively inherited IGHD, including a sporadic case.…”

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: Association with subtype, body-mass index, severity and age of onset

“…Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight (Zigman and Elmquist, 2003). Human ghrelin is a 28-amino acid peptide, its gene is located on chromosome 3p25-26 and consists of four exons and three introns (Wajnrajch et al, 2003). IV administration of ghrelin to healthy humans increases subjective appetite and energy intake from a buffet lunch by 28 % (Wren et al, 2001).…”

GH-Releasing Hormone Receptor Gene: A Novel Splice-Disrupting Mutation and Study of Founder Effects

“…Subsequently, this mutation was identified in several different families from the Indian subcontinent, and a founder effect has been demonstrated [6]. In 1999, Salvatori et al [7] identified the c.57 + 1G>A (IVS1 + 1G>A) GHRHR mutation in 22 patients with IGHD from a large kindred from the region of Itabaianinha in the state of Sergipe in Northeastern Brazil.…”