An investigation of genetic variation in complex disorders of the pituitary gland

摘要: Congenital hypopituitarism can be triggered by environmental insults, such as viral infections, vascular or degenerative damage and exposure to alcohol drugs. Genetic mutations have been identified in genes responsible for pituitary development function, however, only up 10% of patients affected recognised known genes. Clinical phenotypes may arise from gene dosage imbalance, but routine cytogenetic molecular techniques insufficiently sensitive detect chromosome rearrangements that are either submicroscopic size limited a specific genomic locus both. In the present study, ten with complex pathology gland unknown aetiology were clinically pre-selected according criteria checklist, undergo genome-wide screening copy number changes high-resolution 250K SNP array. Genomic sequencing three candidate genes, BARX2, OTX2 BMP4, was carried out larger cohorts selected patients. Three pathogenic imbalances, 6q terminal duplication, 11q deletion, an interstitial deletion 22q detected two patients, breakpoints defined at high resolution. A rearrangement region 1p36.33 found patient presenting association tetralogy Fallot. Two CNVs location cytogenetically visible translocation between chromosomes one patient. One patient, contained whole length ENG gene. novel amino acid change BARX2 isolated hypopituitarism. nonsense mutation associated wth severe eye defects. These findings contribute understanding genetic bases congenital