Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy

Abstract

AbstractBackground:With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year.Methods:Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score <−3) and failed GH stimulation test were studied. Those having concomitant thyroid hormone or cortisol deficiencies were appropriately replaced prior to starting GH treatment. A magnetic resonance imaging (MRI) brain scan was done in all. Genetic mutations were tested for inGH1, GHRH, LHX3, LHX4andPROP1, POU1F1andHESX1genes.Results:Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in theGH1gene. In two children, one each had a mutation inPROP1andLHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygousGH1deletion than in children with no genetic defect.Conclusions:Response to GH at the end of 1 year was poor in children with the homozygousGH1deletion as compared to those withGHRHRmutation or without a known mutation.