Molekulargenetische Untersuchungen zur Rolle des humanen LHX3-Gens bei der menschlichen Hypophysenentwicklung

LHX3 is a LIM-HD protein and plays an important role in the organagenesis of the piitary gland as demonstrated by knock mice experiments. Genetic studys in patients with combined pituitary deficency provides apart from knock out models a tool to improve the knowledge about the transcriptional regulation of the development of the pituitary gland. We isolated genomic DNA of 80 patients with combined pituitary deficiency. Exon-intron boundaries were established by direct sequencing of the human LHX3 cDNA. A SSCP-analysis of the exons was followed by direct sequencing. The LHX3 gene consists of six exons spanning a region of 7.2 kb. We found a high grade of homology between the human and murine LHX3 gene. Two of 80 patients revealed a polymorphism in exon 2 and 3/80 displayed a point mutation in the untranslated region of exon 3.Germline mutations within the lhx3 gene seems to be a rare event in patients with combined pititary deficiency.