Browsing by Subject "oligonucleotide probe"

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    Partial and whole gene deletion mutations of the GCK and HNF1A genes in maturity-onset diabetes of the young
    (2007) Ellard S.; Thomas K.; Edghill E.L.; Owens M.; Ambye L.; Cropper J.; Little J.; Strachan M.; Stride A.; Ersoy B.; Eiberg H.; Pedersen O.; Shepherd M.H.; Hansen T.; Harries L.W.; Hattersley A.T.
    Aims/hypothesis: Heterozygous mutations of glucokinase (GCK) and hepatocyte nuclear factor-1 alpha (HNF1A; also known as hepatic transcription factor 1 [TCF1]) genes are the most common cause of MODY. Genomic deletions of the HNF1B (also known as TCF2) gene have recently been shown to account for one third of mutations causing renal cysts and diabetes syndrome. We investigated the prevalence of partial and whole gene deletions in UK patients meeting clinical criteria for GCK or HNF-1α/-4α MODY and in whom no mutation had been identified by sequence analysis. Methods: A multiplex ligation-dependent probe amplification (MLPA) assay was developed using synthetic oligonucleotide probes for 30 exons of the GCK, HNF1A and HNF4A genes. Partial or whole gene deletions were identified in 1/29 (3.5%) probands using the GCK MLPA assay and 4/60 (6.7%) of probands using the HNF1A/-4A MLPA assay. Four different deletions were detected: GCK exon 2, HNF1A exon 1, HNF1A exons 2 to 10 and HNF1A exons 1 to 10. An additional Danish pedigree with evidence of linkage to HNF1A had a deletion of exons 2 to 10. Testing other family members confirmed co-segregation of the deletion mutations with diabetes in the pedigrees. Conclusions/interpretation: Large deletions encompassing whole exons can cause GCK or HNF-1α MODY and will not be detected by sequencing. Gene dosage assays, such as MLPA, are a useful adjunct to sequence analysis when a diagnosis of MODY is strongly suspected. © 2007 Springer-Verlag.
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    The Factor v G1691A, Factor v H1299R, prothrombin G20210A polymorphisms in children with family history of premature coronary artery disease
    (2009) Çiftdoǧan D.Y.; Coşkun Ş.; Ulman C.; Tkz H.
    Atherosclerosis, the major cause of coronary artery disease (CAD), has a very long asymptomatic development phase, which begins in childhood. In this study, we describe the Factor V G1691A, Factor V H1299R and prothrombin G20210A gene polymorphisms in children with a family history of premature CAD. Evidence of these polymorphisms in these children may predict the probability of having atherosclerosis in the future. Our study included a total of 140 children, 72 males and 68 females between the ages of 4.9 and 15.7 years. Among these children, 73 had a parental history of premature CAD and the remaining 67 belonged to our control group. The participants were screened for the mutations Factor V G1691A, Factor V H1299R and prothrombin G20210A by polymerase chain reaction amplified DNA products with specific oligonucleotide probes. Our results suggested that frequencies of the mutated allele of Factor V G1691A and prothrombin G20210A are higher in children with a parental history of premature CAD. In conclusion, Factor V G1691A and prothrombin G20210A polymorphisms which were detected in higher frequencies in children with a parental history of premature CAD may indicate a risk for developing atherosclerosis and might be useful in screening for CAD in children; however, large population-based research is necessary to investigate further genetic risk assessment for CAD. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.