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Growth hormone receptor ( GHR ) gene polymorphism and prader–willi syndrome
Author(s) -
Butler Merlin G.,
Roberts Jennifer,
Hayes Jena,
Tan Xiaoyu,
Manzardo Ann M.
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35980
Subject(s) - growth hormone receptor , endocrinology , medicine , allele , growth hormone treatment , failure to thrive , obesity , biology , polymorphism (computer science) , short stature , hormone , growth hormone , genetics , gene
Prader–Willi syndrome (PWS) is a genomic imprinting disorder due to loss of paternally expressed genes in the 15q11–q13 region and characterized by hypotonia, a poor suck, failure to thrive, hypogonadism/hypogenitalism, growth hormone deficiency, learning, and behavioral problems and hyperphagia leading to early childhood obesity. Growth hormone acts as a ligand for the growth hormone receptor (GHR) coded by a gene polymorphic for an exon‐3 deletion ( d3 ) seen in about 50% of Caucasians and associated with an increased response to growth hormone (GH) therapy. We examined 69 individuals with PWS (average age ± SD = 20.1 ± 12.8 year). The GHR allele distribution in our PWS subjects was similar to reported data in the literature with no gender or PWS genetic subtype differences. A negative correlation was found with age for height standard deviational scores and a positive correlation with age for weight and BMI for non‐GH treated PWS subjects. Adjusting for effects of age and gender, individuals with PWS and the d3 / d3 allele showed a significant increase in BMI compared with those having the full length ( fl ) allele. In addition, 12 infants and children with PWS were examined when growth and GH data were available before and during GH treatment. A significant increase in growth rate (1.7 times) was noted in the presence of the d3 allele ( fl / fl = 0.87 cm/month; fl / d3 or d3 / d3 = 1.5 cm/month; P < 0.05). The presence of the d3 allele and its impact on growth and medical care of individuals with PWS while on GH therapy should be further investigated. © 2013 Wiley Periodicals, Inc.