title: A novel splicing mutation in exon 4 (456G>A) of the GH1 gene in a patient with congenital isolated growth hormone deficiency.
abstract: Isolated Growth Hormone Deficiency (IGHD) due to GH1 gene defects has a variable inheritance pattern: autosomal recessive, autosomal dominant, and X-linked. the autosomal dominantly inherited form, IGHD II, is mainly caused by heterozygous mutations of splicing around the exon 3/IVs3 boundary region of the GH1 gene resulting in exon 3 skipping of transcripts. We have previously reported findings on GH1 gene mutations in 28 russian patients with severe congenital IGHD (-3.22+/-1.2 height sDs at the age of 1yr); five heterozygous dominant negative splice site mutations in intron 2, intron 3, and exon 4 of the GH1 gene were identified in 32.1% of the cohort. In the present report we describe a novel 456G>A heterozygous mutation of splicing of the last base of the 3'-acceptor splice site of exon 4 within the GH1 in a 4.2-year old, extremely short (-5.32 height sDs) girl with congenital IGHD. the mutation involves a highly conserved GGGgtg sequence of the exon 4/IVs4 boundary region of the GH1 gene. the predicted effect of the 456 G>A mutation is perturbed splicing with possible skipping of exon 4 of the GH1 gene. the novel heterozygous 456 G>A mutation in exon 4 expands the spectrum of dominant negative splicing defects within the GH1 gene, responsible for congenital IGHD.
authors.affiliation: Institute of Pediatric Endocrinology, Endocrinology Research Center, Russian Academy of Medical Sciences, Moscow, Russia. olga-vf@yandex.ru
authors.forename: Olga V
authors.initials: OV
authors.lastname: Fofanova
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Evgrafov
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Polyakov
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Peterkova
authors.forename: Ivan I
authors.initials: II
authors.lastname: Dedov
mesh_terms: D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004393:Dwarfism, Pituitary / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D013006:Growth Hormone / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012313:RNA / Q000235:genetics; D022821:RNA Splice Sites
chemical_list: D022821:RNA Splice Sites; D012313:RNA; D013006:Growth Hormone; D004247:DNA