Frequency of mutations in the GnRH receptor gene in pakistani patients with hypogonadotropic hypogonadism

The hypothalamic gonadotropic releasing hormone (gnrh) is a key regulator in normal puberty,sexual development and function. the proper binding of gnrh to its receptor,gnrhr,is necessary for normal secretion of gonadotropins. the deficiency in release or action of gnrh leads to hypogonadotropic hypogonadism (hh) characterized by low follicle stimulating hormone (fsh),luteinizing hormone (lh) and estradiol (e2) and results in absent or impaired sexual development at puberty. there are about 20 genes identified as possible regulator of puberty. the mutations in gnrh1 and gnrhr are possible causes of hh. the present study was designed to identify mutations in gnrh1 and gnrhr genes and their correlation with hh in pakistani girls. fifty two hh patients and fifty two age matched controls were included in the study. genomic dna was extracted and amplified by pcr using specific primers for gnrh1 and gnrhr exons. mutations were analyzed by sanger sequencing. no mutation was identified in gnrh1 gene,while two mutations in gnrhr gene were observed in one sporadic case of isolated hh. the first was a synonymous substitution mutation of t to c at nucleotide position 221,which does not result in the alteration of coded amino acid residue,histidine. the other was missense mutation determined at nucleotide position 101,which results in the substitution of serine with phenylalanine at 34th position of the extracellular domain of gnrhr. in conclusion,the present study demonstrates that mutations in gnrhr may play an important role in delaying puberty in the local population. copyright 2015 zoological society of pakistan.