Molecular analysis of the PROP1 gene in the cohort of Turkish patients with Combined Pituitary Hormone Deficiency

Abstract

Combined pituitary hormone deficiency (CPHD) designatesimpaired production of growth hormone (GH) and one ormore of the other anterior pituitary hormones. The extent ofthe symptoms depends upon the degree and the combinationof the deficient hormones. Most affected children have normalor low birth weight and birth length, and an uncomplicatedperinatal period. Growth failure and failure to thrive generallystart in infancy or early childhood. Rarely, hypothyroidism isthe presenting finding. Some cases may show severe mentalretardation. Studies show that up to 50% of CPHD cases aregenetically derived and approximately half of these are causedby PROP1 gene mutations. Other genes, POU1F1, HESX1,LHX3 and LHX4, may rarely be associated with familialCPHD. We ascertained 50 pedigrees with variable degrees ofCPHD from pediatric endocrinology clinics throughout Turkey.Screenings were conducted for PROP1 mutations by MultiplexLigation-dependent Probe Amplification (MLPA) toidentify if any gross deletions followed by DNA sequencingfor other small variation and mutations. Our molecular investigationis presently in progress. During the poster session, wepropose to present the PROP1 gene mutation spectrum andcontribute to enlighten the mutation detection rate of PROP1in Turkish CPHD patients. Although, it is known that clinicalphenotype of PROP1 deficiency is variable – even among individualswith the same mutation – making the genotytpe-phenotypecorrelation difficult, early molecular diagnosis ofaffected families will provide private genetic counseling, earlymanagement of the hormonal deficiencies and correct differentialdiagnosis.