title: GH-1 gene splicing mutations: molecular basis of hereditary isolated growth hormone deficiency in children.
abstract: Children, residents of the Russian Federation, with congenital isolated growth hormone deficiency, were screened for mutations of GH-1 gene, the main gene of this deficiency. Twenty-eight children from 26 families with total congenital isolated growth hormone deficiency were examined. Direct sequencing of GH-1 detected five splicing mutations in intron 2, intron 3, and exon 4, two of them were never described previously. Three dominant negative mutations of GH-1 splicing, the basis for autosomal dominant isolated growth hormone deficiency (type II), are presented: IVS2 -2A>T, IVS3 +2T>C, and IVS3 +1G<A. GH-1 is the main gene of type II isolated growth hormone deficiency in patients living in the Russian Federation. All detected mutations of GH-1 impair splicing processes, which distinguishes them from mutations in other forms of isolated growth hormone deficiency. The detected variety of GH-1 splicing mutations attests to allele genetic heterogeneity of this pathology. The "hot spot" of mutations is 5'-donor splicing site of GH-1 intron 3, while IVS3 +IG>A mutation can be regarded as the most incident in type II isolated growth hormone deficiency in the Russian population.
authors.affiliation: Endocrinological Research Center, Russian Academy of Medical Sciences. olga-vf@yandex.ru
authors.forename: O V
authors.initials: OV
authors.lastname: Fofanova
authors.forename: O V
authors.initials: OV
authors.lastname: Evgrafov
authors.forename: A V
authors.initials: AV
authors.lastname: Polyakov
authors.forename: V A
authors.initials: VA
authors.lastname: Peterkova
authors.forename: I I
authors.initials: II
authors.lastname: Dedov
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D005260:Female; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D012326:RNA Splicing
chemical_list: D017931:DNA Primers; D013006:Growth Hormone