• Journal of Genetic Medicine
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• v.7 no.1
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• pp.1-8
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• 2010

Hemophilia A is a sex-linked recessive coagulation disorder associated with diverse mutations of the factor VIII gene and a variety of phenotypes. The type of mutation involved dictates the activity of factor VIII, and in turn the severity of bleeding episodes and development of alloantibodies against factor VIII (inhibitors). Missense mutations are the most common genetic risk factors for hemophilia A, especially mild to moderate cases, but carry the lowest risk for inhibitor development. On the other hand, intron 22 inversion is the most common mutation associated with severe hemophilia A and is associated with high risk of inhibitor formation. Large deletions and nonsense mutations are also associated with high risk of inhibitor development. Additional mutations associated with hemophilia A include frameshift and splice site mutations. It is therefore valuable to assess the mutational backgrounds of hemophilia A patients in order to to interpret their symptoms and manage their health problems.

• Journal of Interdisciplinary Genomics
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• v.4 no.1
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• pp.15-18
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• 2022

Hemophilia A is a rare X-linked congenital deficiency of clotting factor VIII (FVIII) that is traditionally diagnosed by measuring FVIII activity. Various mutations of the FVIII gene have been reported and they influence on the FVIII protein structure. A deficiency of or reduction in FVIII protein manifests as spontaneous or induced bleeding depending on the disease severity. Mutations of the FVIII gene provide important information on the severity of disease and inhibitor development. FVIII mutations also affect the discrepant activities found using different FVIII assays. FVIII activity is affected differently depending on the mutation site. Long-range PCR is commonly used to detect intron 22 inversion, the most common mutation in severe hemophilia. However, point mutations are also common in patients with hemophilia, and direct Sanger sequencing and copy number variant analysis are being used to screen for full mutations in the FVIII gene. Advances in molecular genetic methods, such as next-generation sequencing, may enable accurate analysis of mutations in the factor VIII gene, which may be useful in the diagnosis of mild to moderate hemophilia. Genetic analysis is also useful in diagnosing carriers and managing bleeding control. This review discusses the current knowledge about mutations in hemophilia and focuses on the clinical aspects associated with these mutations and the importance of genetic analysis.

• Molecules and Cells
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• v.37 no.5
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• pp.372-382
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• 2014

In this study, the chloroplast (cp) genome sequences from three early diverged leptosporangiate ferns were completed and analyzed in order to understand the evolution of the genome of the fern lineages. The complete cp genome sequence of Osmunda cinnamomea (Osmundales) was 142,812 base pairs (bp). The cp genome structure was similar to that of eusporangiate ferns. The gene/intron losses that frequently occurred in the cp genome of leptosporangiate ferns were not found in the cp genome of O. cinnamomea. In addition, putative RNA editing sites in the cp genome were rare in O. cinnamomea, even though the sites were frequently predicted to be present in leptosporangiate ferns. The complete cp genome sequence of Diplopterygium glaucum (Gleicheniales) was 151,007 bp and has a 9.7 kb inversion between the trnL-CAA and trnV-GCA genes when compared to O. cinnamomea. Several repeated sequences were detected around the inversion break points. The complete cp genome sequence of Lygodium japonicum (Schizaeales) was 157,142 bp and a deletion of the rpoC1 intron was detected. This intron loss was shared by all of the studied species of the genus Lygodium. The GC contents and the effective numbers of codons (ENCs) in ferns varied significantly when compared to seed plants. The ENC values of the early diverged leptosporangiate ferns showed intermediate levels between eusporangiate and core leptosporangiate ferns. However, our phylogenetic tree based on all of the cp gene sequences clearly indicated that the cp genome similarity between O. cinnamomea (Osmundales) and eusporangiate ferns are symplesiomorphies, rather than synapomorphies. Therefore, our data is in agreement with the view that Osmundales is a distinct early diverged lineage in the leptosporangiate ferns.

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.89-94
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• 2018

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is inherited microangiopathy caused by mutations in the Notch3 gene. Typical findings from brain magnetic resonance imaging (MRI) include subcortical lacunes, extensive white matter change and cerebral microbleeds(CMBs). CMBs are indicative of bleeding-prone microangiopathy. Despite some studies investigating the association between lacunes and cognitive dysfunction in CADASIL, few studies have examined the relationship between cognitive dysfunction and CMBs. We sought to assess whether CMBs are associated with cognitive dysfunction in CADASIL. This study enrolled 83 consecutive patients with CADASIL between April 2012 and January 2014. Their degree of cognitive dysfunction was assessed by the Korean version of the CERAD neuropsychological assessment battery, digit span test, and the Stroop test. A 3.0-T MRI was used to obtain T1-weighted, fluid-attenuated inversion recovery, and susceptibility weighted images. In multiple logistic regression analysis, the grade of CMBs influenced tests of memory dysfunction (p=0.003). Three or more lacunes correlated with dysfunction in the executive domain (p=0.013) and attention domain (p=0.005). White matter hyperintensity (WMH) was an independent predictor of executive dysfunction (p=0.001). These findings suggest that in addition to lacunes, CMBs and WMHs may be useful imaging markers to associated with cognitive dysfunction in CADASIL.