Growth hormone receptor (GHR) gene polymorphism and Prader-Willi syndrome.

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.