title: A novel and de novo splice-donor site mutation in intron 3 of the GH-1 gene in a patient with isolated growth hormone deficiency.
abstract: Heterozygous mutations at the splice-donor site of inron 3 of the GH-1 gene are known to affect growth hormone (GH) mRNA splicing and cause isolated GH deficiency (IGHD), which is inherited in an autosomal dominant trait. We report here a novel and de novo heterozygous IVS3 + 6T --> G mutation of the GH-1 gene in a Japanese patient with IGHD. RT-PCR analyses of the GH-1 minigene transcripts demonstrated that the IVS3 + 6T --> G mutation causes complete skipping of exon 3. We found a heterozygous IVS4 + 18G --> T polymorphism of the GH-1 gene in the patient, which was shared by the father, but not by the mother. Sequencing of individual alleles of the patient's GH-1 gene confirmed that the IVS3 + 6T --> G mutation and the IVS4 + 18G --> T polymorphism exist on the same chromosome. These findings indicate that the IVS3 + 6T --> G mutation arose in a germ cell of the father and caused IGHD in the patient.
authors.affiliation: Department of Endocrinology and Metabolism, National Children's Medical Research Center, Tokyo 154-8509, Japan. nkatsumata@nch.go.jp
authors.forename: N
authors.initials: N
authors.lastname: Katsumata
authors.forename: S
authors.initials: S
authors.lastname: Matsuo
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; D019382:Human Growth Hormone; D004247:DNA