Abstract
Growth hormone deficiency (GHD) results from variations affecting the production and
release of growth hormone (GH) and is of 2 types: isolated growth hormone deficiency
(IGHD) and combined pituitary hormone deficiency (CPHD). IGHD results from mutations
in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1, and HESX1. The present study reports on screening of POU1F1, PROP1, and HESX1 in CPHD patients and the novel variations identified. Fifty-one CPHD patients from
49 unrelated families clinically diagnosed on the basis of biochemical and imaging
investigations along with 100 controls were enrolled. Detailed family history was
noted from all participants and 5 ml blood samples drawn were processed for DNA isolation
followed by direct sequencing of POU1F1, PROP1, and HESX1genes. Of the 51 patients, 8 were females and 43 were males. Mean height standard
deviation score (SDS) and weight SDS were −5.50 and −2.76, respectively. Thirty-six
of the 51 patients underwent MRI of which 9 (25%) had normal pituitary structure and
morphology while 27 (75%) showed abnormalities. Molecular analysis revealed 10 (20%)
patients to have POU1F1 and PROP1 mutations/variations of which 5 were novel and 2 previously reported. No mutations
were identified in HESX1. The novel variations identified were absent in the 100 healthy individuals screened
and the control database Exome Aggregation Consortium (ExAC). Reported POU1F1 and PROP1 mutation hotspots were absent in our patients. Instead, novel POU1F1 changes were identified suggesting existence of a distinct mutation spectrum in our
population.
Key words
CPHD - genetics - mutations - novel findings
