Ege University Faculty of Medicine, Division of Pediatric Genetics, İzmir, Turkey**
Ege University Faculty of Medicine, Department of Medical Genetics, İzmir, Turkey***
Ege University Faculty of Medicine, Division of Pediatric Endocrinology, İzmir, Turkey****
Konya Education and Research Hospital, Clinic of Pediatric Endocrinology, Konya, Turkey
Combined pituitary hormone deficiency (CPHD) is characterized by the impaired production of GH together with one or more of other pituitary hormones. The most commonly recognized genetic defects associated with CPHD include mutations within PROP1, POU1F1, HESX1, LHX3, LHX4, OTX2, GLI2, and SOX3. The phenotype connected to POU1F1 mutations is characterized by profound GH and PRL deficiencies, variable degrees of TSH deficiency, severe proportional short stature, atypical facies, and feeding difficulties in infancy. Patients harboring mutations within PROP1 gene present with GH, PRL, and TSH deficiencies in addition to variable defects in luteinizing hormone/follicle-stimulating hormone and adrenocorticotropic hormone secretion. PROP1 mutations are the most common known genetic cause of CPHD cases.
Here, we present 3 cases with POU1F1 mutation and 1 case with PROP1 mutation, who were molecularly diagnosed in Medical Genetics Department of Ege University.
The three cases (1 female, 2 males) carrying POU1F1 mutations all had short stature. One male case with a novel mutation, p.K216T, also presented with micropenis in addition to short stature. The other mutations detected in POU1F1 gene were S50A, R265W; S50A being novel. The case with PROP1 mutation also had short stature and micropenis. Molecular analysis revealed a frameshift p.L102CfsX8 mutation in the PROP1 gene. Biochemical testing showed PRL and GH deficiencies in all cases. Two cases with POU1F1 defect and the case with PROP1 defect also had central hypothyroidism.
It is considered that in patients with growth retardation together with combined pituitary hormone deficiency, POU1F1 and PROP1 gene mutations should be investigated. In this study, two novel POU1F1 mutations were detected for the first time.