title: A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica.
abstract: LIM homeodomain transcription factors regulate many aspects of development in multicellular organisms. LHX4/Lhx4 is a protein that is essential for pituitary development and motor neuron specification in mammals. In human, a heterozygous splicing mutation of the LHX4 gene was reported in a family with combined pituitary hormone deficiencies (CPHD). In addition to CPHD, these patients were characterized by small sella turcica and chiari malformation. Here we report a Japanese patient with CPHD (GH, PRL, TSH, LH, FSH, and ACTH deficiency) due to a novel missense mutation (P366T) of the LHX 4 gene. She showed severe respiratory disease and hypoglycemia soon after birth. Brain MRI demonstrated hypoplastic anterior pituitary, ectopic posterior lobe, a poorly developed sella turcica, and chiari malformation. Sequence analysis of the LHX 4 gene identified a heterozygous missense mutation (P366T) in exon 6, which was present in LIM4 specific domain. Neither of the patient's parents harbored this mutation, indicating de novo mutation.
authors.affiliation: Department of Pediatrics, Hokkaido University School of Medicine, N15, W7, Sapporo 060-0835, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Hattori
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakajima
authors.forename: Koji
authors.initials: K
authors.lastname: Okuhara
authors.forename: Junko
authors.initials: J
authors.lastname: Tsubaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujieda
mesh_terms: D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007018:Hypopituitarism / Q000151:congenital / Q000235:genetics* / Q000473:pathology*; D007223:Infant; D060850:LIM-Homeodomain Proteins; D008279:Magnetic Resonance Imaging; D020125:Mutation, Missense; D009778:Occipital Lobe / Q000002:abnormalities* / Q000473:pathology; D010903:Pituitary Gland, Anterior / Q000002:abnormalities* / Q000473:pathology; D010907:Pituitary Hormones / Q000172:deficiency; D012658:Sella Turcica / Q000002:abnormalities* / Q000473:pathology; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C486362:LHX4 protein, human; D060850:LIM-Homeodomain Proteins; D010907:Pituitary Hormones; D014157:Transcription Factors