Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency

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 and while CPHD is associated with defects in transcription factor genes ,, and The present study reports on screening of, , and 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 ,, and genes. 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 and mutations/variations of which 5 were novel and 2 previously reported. No mutations were identified in The novel variations identified were absent in the 100 healthy individuals screened and the control database Exome Aggregation Consortium (ExAC). Reported and mutation hotspots were absent in our patients. Instead, novel changes were identified suggesting existence of a distinct mutation spectrum in our population.

Etiology of Hypopituitarism in Adult Patients: The Experience of a Single Center Database in the Serbian Population

“…However, with increasing knowledge about the etiology of hypopituitarism, nontumoral causes are becoming more evident [4]. In the recent years, new gene mutations affecting hypothalamo/pituitary embryogenesis have been revealed, and novel genetic causes of congenital hypopituitarism [5, 6] have been identified.…”

Characterization of a Novel POU1F1 Mutation Identified on Screening 160 Growth Hormone Deficiency Patients

“…Our previous study was conducted with a broad aim to ensure a widespread analysis of the genomic regions including the whole GH1 gene deletion, the GH1 promoter, and all 5 GH1 exons along with complete screening (13 exons) of the GHRHR gene in IGHD patients and all the coding exons of PROP1, POU1F1, and HESX1 in CPHD patients. The detailed findings on the molecular screening in IGHD and CPHD were reported separately [7,8]. In the present study, we build on our previous findings where several known and novel mutations were identified.…”

“…Participants were recruited as described previously [7,8]. Briefly, a total of 160 consecutive patients, diagnosed with IGHD or CPHD were recruited from the Pediatric and Adolescence Endocrine Clinic (PAEC); Department of Endocrinology & Metabolism, Pediatric Endocrine Clinic (PEC); Department of Pediatrics, AIIMS, New Delhi; and Department of Endocrinology and Metabolism, Army Hospital (Referral & Research, New Delhi).…”

“…Briefly, a total of 160 consecutive patients, diagnosed with IGHD or CPHD were recruited from the Pediatric and Adolescence Endocrine Clinic (PAEC); Department of Endocrinology & Metabolism, Pediatric Endocrine Clinic (PEC); Department of Pediatrics, AIIMS, New Delhi; and Department of Endocrinology and Metabolism, Army Hospital (Referral & Research, New Delhi). Diagnosis was based on clinical, biochemical, and imaging investigations as described previously [7,8]. The study protocol adhered to the tenets of Declaration of Helsinki and was approved by the AIIMS Ethics Committee, New Delhi.…”

“…Informed written consent was taken from all the participants prior to inclusion in the study. Detailed pedigree information and blood samples were collected from 160 trios (patients and their parents), available family members and 100 controls all of whom belonged to the North, North Western, Central and North Eastern regions of India [7,8].…”