ABSTRACT
ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.
ABSTRACT
The LHX3 and LHX4 LIM-homeodomain transcription factors play essential roles in pituitary gland.Nervous system developments play certain roles in some cancers,leukemia,and deafness disease.Mutations in the genes encoding these regulatory proteins are closely associated with combined hormone deficiency diseases in human and animal models,and related to nervous system defect,tumors,leukemia and deafness.Analysis of these diseases and the biochemical properties of the LHX3 and LHX4 protein will facilitate a better understanding of the pathogenesis of these diseases.LHX3 and LHX4 are reviewed in this paper.