title: Screening for mutations in the promoter and the coding region of the IGFBP1 and IGFBP3 genes in Silver-Russell syndrome patients.
abstract: In the present study we sought to identify genetic variation in genes for insulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12-13 which through alteration of protein function or level of expression might contribute to the manifestation of Silver-Russell syndrome. Genomic DNA samples from 49 Silver-Russell syndrome (SRS) patients and from unaffected controls were investigated by single-strand conformation analysis. Overlapping polymerase chain reaction fragments covered the whole coding sequences as well as the 5' untranslated region of the IGFBP1 and IGFBP3 genes. We detected 3 new polymorphisms in the transcribed sequence of IGFBP1, one amino acid polymorphism in exon 1 of IGFBP3 and four variants in its promotor region and in intron 1. They all occurred in similar frequencies in SRS patients and in controls. Thus, paternally inherited mutations in the promoter and coding regions of IGFBP1 and IGFBP3 genes play neither a major nor a minor role in the etiology of SRS. The newly detected polymorphisms in the coding region are powerful tools for analysis of imprinting status and for detection of possible changes in the imprinting patterns of the two genes.
authors.affiliation: Division of Clinical Genetics, Institute of Anthropology and Human Genetics, University of Tübingen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Eggermann
authors.forename: H A
authors.initials: HA
authors.lastname: Wollmann
authors.forename: J
authors.initials: J
authors.lastname: Tomiuk
authors.forename: M B
authors.initials: MB
authors.lastname: Ranke
authors.forename: P
authors.initials: P
authors.lastname: Kaiser
authors.forename: T
authors.initials: T
authors.lastname: Eggermann
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005796:Genes / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006130:Growth Disorders / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics*; D009154:Mutation; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D013577:Syndrome
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D004247:DNA