title: A novel mutation in PIT-1: phenotypic variability in familial combined pituitary hormone deficiencies.
abstract: Mutations in PIT-1 have been described in several cases of familial combined pituitary hormone deficiencies. This study describes a novel PIT-1 mutation that was found in two siblings of a highly consanguineous family of Israeli-Arab origin. The missense mutation (G688A) causes a lysine (K) to glutamic acid (E) substitution at codon 230. This codon resides in the first helix of the POU-homeodomain, which is directly involved in DNA binding. This amino acid is conserved in most homeodomain proteins, suggesting that the substitution disrupts the DNA-binding activity of the mutant protein. Two main observations are described: 1. The clinical presentation of the mutation involves intrauterine growth retardation. 2. One sibling had full deficency of growth hormone and thyroid stimulating hormone, whereas the other had only growth hormone deficiency. This is, to the best of our knowledge, a unique expression of a novel PIT-1 mutation.
authors.affiliation: Felsenstein Medical Research Center and Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva. gyablonski@clalit.org.il
authors.forename: G
authors.initials: G
authors.lastname: Gat-Yablonski
authors.forename: L
authors.initials: L
authors.lastname: Lazar
authors.forename: A
authors.initials: A
authors.lastname: Pertzelan
authors.forename: M
authors.initials: M
authors.lastname: Phillip
mesh_terms: D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D010641:Phenotype; D010907:Pituitary Hormones / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D004247:DNA