title: Low prevalence of insulin-like growth factor-I gene mutations in human growth disorders.
abstract: In an attempt to identify genetic lesions contributing to human growth disorders, we evaluated a prospectively recruited group of children with growth failure for mutations in the insulin-like growth factor-I (IGF-I) gene. Two complementary approaches were used: Southern blot analysis to examine the large scale organization of the gene, and a solution hybridization, nuclease protection assay to identify small alterations, such as point mutations. From a total of 61 subjects studied, 52 had no organic basis for their short stature. Analysis of chromosomal DNA from these individuals failed to reveal any variation in the IGF-I gene except for a HindIII site polymorphism which maps near the 3' end of the last IGF-I exon. No single nucleotide substitutions were found within IGF-I-coding regions. Since the frequency of the length polymorphism was the same for both normal-sized and short individuals, it is unlikely to be associated with growth abnormalities. Our results suggest that there is minimal DNA sequence variability in the human IGF-I gene and that mutations in IGF-I exons are infrequent causes of growth failure.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: R
authors.initials: R
authors.lastname: Lajara
authors.forename: J P
authors.initials: JP
authors.lastname: Galgani
authors.forename: D P
authors.initials: DP
authors.lastname: Dempsher
authors.forename: D M
authors.initials: DM
authors.lastname: Bier
authors.forename: P
authors.initials: P
authors.lastname: Rotwein
mesh_terms: D015139:Blotting, Southern; D002648:Child; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis*; D004262:DNA Restriction Enzymes; D004393:Dwarfism, Pituitary / Q000097:blood / Q000235:genetics*; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D009154:Mutation; D015345:Oligonucleotide Probes; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000032:analysis*; D013002:Somatomedins / Q000235:genetics*
chemical_list: D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D004247:DNA; D004262:DNA Restriction Enzymes