RARITY OF PIT1 INVOLVEMENT IN CHILDREN FROM RUSSIA WITH COMBINED PITUITARY-HORMONE DEFICIENCY

To ascertain the molecular background of combined pituitary hormone de ficiency, screening for mutations in the pituitary-specific transcript ion factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 c hildren from Russia with combined growth hormone (GH)/prolactin (Prl)/ thyroid-stimulating hormone (TSH) deficiency. The group of patients, s uspected of PIT1 mutations, consisted of four familial cases (seven pa tients) and eight sporadic cases. All had complete GH deficiency and c omplete or partial Prl and TSH deficiency. Direct sequencing of all si x exons of PIT1 and its promoter region showed a C to T transition mut ation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L), The pat ient was heterozygous for mutant and normal alleles, The heterozygous P14L mutation was also present in her mother as well as in her materna l aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluat ion of genomic imprinting. In other children of our series, no mutatio n in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian chil dren with GH/Prl/TSH deficiency. However, as the involvement of PIT1 m utation is rare in Russia, the other negative cases need to be analyze d for another candidate gene responsible for combined GH/Prl/TSH defic iency. (C) 1998 Wiley-Liss, Inc.