Endocrine Abstracts

Familial isolated growth hormone deficiency is exceedingly rare. We present two siblings of non-consanguineous parents with this syndrome and describe their response to growth hormone therapy. We have also carried out a mutational analysis of their GH1 and GHRH-R genes.

A mutation scan of the entire coding region and flanking intronic sequences of GH-1 and GHRH-R was undertaken in both index cases and parents. GH1 and GHRH-R mutational analysis did not reveal any pathogenic mutations in either the coding regions or the intron–exon boundary regions.

We then analysed the 5′UTR of GH-1 and found that the father, siblings 1 and 2 have a deletion SNP in the 5′UTR of GH-1 – rs11568827. We also found that the mother, siblings 1 and 2 have an SNP in the 5′ UTR of GH-1 – rs11568828.

SNPs in the 5′UTR have been implicated in the causation of numerous diseases, and the combination of several SNPs in promoter regions of GH-1 can affect functional sequences in adults. As our kindred have no family history we hypothesise that IGHD in this kindred is caused by the interplay of two SNPs of the 5′UTR of GH-1, one inherited from each parent, which has not been previously reported.