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Novel Splice Site Mutation (novel + splice_site_mutation)
Selected AbstractsUsing a minigene approach to characterize a novel splice site mutation in human F7 gene causing inherited factor VII deficiency in a Chinese pedigreeHAEMOPHILIA, Issue 6 2009T. YU Summary., Factor VII deficiency which transmitted as an autosomal recessive disorder is a rare haemorrhagic condition. The aim of this study was to identify the molecular genetic defect and determine its functional consequences in a Chinese pedigree with FVII deficiency. The proband was diagnosed as inherited coagulation FVII deficiency by reduced plasma levels of FVII activity (4.4%) and antigen (38.5%). All nine exons and their flanking sequence of F7 gene were amplified by polymerase chain reaction (PCR) for the proband and the PCR products were directly sequenced. The compound heterozygous mutations of F7 (NM_000131.3) c.572-1G>A and F7 (NM_000131.3) c.1165T>G; p.Cys389Gly were identified in the proband's F7 gene. To investigate the splicing patterns associated with F7 c.572-1G>A, ectopic transcripts in leucocytes of the proband were analyzed. F7 minigenes, spanning from intron 4 to intron 7 and carrying either an A or a G at position -1 of intron 5, were constructed and transiently transfected into human embryonic kidney (HEK) 293T cells, followed by RT-PCR analysis. The aberrant transcripts from the F7 c.572-1G>A mutant allele were not detected by ectopic transcription study. Sequencing of the RT-PCR products from the mutant transfectant demonstrated the production of an erroneously spliced mRNA with exon 6 skipping, whereas a normal splicing occurred in the wide type transfectant. The aberrant mRNA produced from the F7 c.572-1G>A mutant allele is responsible for the factor VII deficiency in this pedigree. [source] Erratum: A novel splice site mutation (3157+1G>T) in the dystrophin gene causing total exon skipping and DMD phenotype ,,HUMAN MUTATION, Issue 6 2001M. Sironi Abstract Erratum: An error was printed in the original version of this article in the Comments section, paragraph 2, relating to the size of exon 22 and the RT-PCR product size described as resulting from the mutation 3157+1G>T. The paragraph should read: "We report a case of a 5 year old DMD patient with a novel splice site mutation affecting the GT dinucleotide splice donor of exon 22. The RT-PCR analysis with primer sets spanning dystrophin exons 17-25 amplified no normal size fragment (1251 bp), but a product shorter by 146 bp (the length of exon 22). Direct sequencing of the faster migrating fragment revealed total skipping of exon 22." [source] One novel and one recurrent mutation in the PROS1 gene cause type I protein S deficiency in patients with pulmonary embolism associated with deep vein thrombosisAMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2006Kazuhiro Mizukami Abstract We investigated the molecular basis of type I protein S (PS) deficiency in two unrelated Japanese families, in which both probands developed pulmonary embolism associated with deep vein thrombosis. Nucleotide sequencing of amplified DNA revealed distinct point mutations in the PROS1 gene of the probands, which were designated protein S Sapporo 1 and protein S Sapporo 2. Additional mutations in the PROS1 gene were excluded by DNA sequencing of all exons and intron/exon boundaries. In the 25-year-old Japanese male patient who carried protein S Sapporo 1, we identified a heterozygous A-to-T change in the invariant ag dinucleotide of the acceptor splice site of intron f of the PROS1 gene. This mutation is a novel splice site mutation that impairs normal mRNA splicing, leading to exon 7 skipping, which was confirmed by platelet mRNA analysis. Translation of this mutant transcript would result in a truncated protein that lacks the entire epidermal growth factor-like domain 3 of the PS molecule. In a 31-year-old Japanese male and his younger brother who each carried protein S Sapporo 2, we detected a previously described heterozygous T-to-C transition at nucleotide position 1147 in exon 10 of the PROS1 gene, which predicts an amino acid substitution of tryptophan by arginine at residue 342 in the laminin G1 domain of the PS molecule. Both mutations would cause misfolding of the PS protein, resulting in the impairment of secretion, which is consistent with the type I PS deficiency phenotype. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Mutations in sarcomeric protein genes not only lead to cardiomyopathy but also to congenital cardiovascular malformationsCLINICAL GENETICS, Issue 1 2008Marja W. Wessels Noncompaction of the ventricular myocardium is associated with de novo mutation in the beta-myosin heavy chain gene Budde et al. (2007) PLoS ONE 2: e1362 Homozygosity for a novel splice site mutation in the cardiac myosin-binding protein C gene causes severe neonatal hypertrophic cardiomyopathy Xin et al. (2007) Am J Med Genet 143: 2662,2667 Alpha-cardiac actin mutations produce atrial septal defects Matsson et al. (2008) Hum Mol Genet 17: 256,265 [source] | |||||||||||||