Mutations within The Transcription Factor PROP1 in a Cohort of Turkish Patients with Combined Pituitary Hormone Deficiency

Objective: Mutations of genes encoding transcription factors which play important roles in pituitary morphogenesis, differentiation and maturation lead to combined pituitary hormone deficiency (CPHD). PROP1 gene mutations are reported as the most frequent genetic aetiology of CHPD. The aim of this study is to describe phenotype of Turkish CPHD patients and define frequency of PROP1 mutations. Methods: Fifty-seven CPHD patients from 50 families were screened for PROP1 mutations. The patients were affected by growth hormone and additional anterior pituitary hormone deficiencies. Results: All patients had GH deficiency, 98,2% had central hypothyroidism, 45,6% had hypogonadotropic hypogonadism, 43,8% had ACTH deficiency and 7,1% had prolactin deficiency. Parental consanguinity rate was 50.9%. 14 cases were familial. Mean height standard deviation score (SDS) and weight SDS were -3,8 (+/-1,4) and -3,1 (+/-2,0), respectively. Of 53 patients with available pituitary imaging, 32 showed abnormalities. None had extra-pituitary abnormalities. 8 index patients had PROP1 gene mutations. Five sporadic patients had homozygous c.301_302delAG (p.Leu102CysfsTer8) mutation, two siblings had exon 2 deletion, two siblings had complete gene deletion and two siblings had homozygous, novel c.353A>G (p.Q118R) mutation. Conclusion: Phenotype of patients regarding hormonal deficiencies, pituitary morphology, presence of extra-pituitary findings, family history of CPHD and parental consanguinity are important to decide which pituitary transcription factor deficiency should be investigated. The frequency of the PROP1 mutations was 16% in our cohort. Mutation rate was higher in familial cases compared to sporadic cases (42,8% vs. 11,6%). PROP1 mutation frequencies vary in different populations and its prevalence is high in Turkish CPHD patients.