Publications (110) View all
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Article: Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia.
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ABSTRACT: Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders-CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF.The American Journal of Human Genetics 04/2013; · 10.60 Impact Factor -
Article: Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome.
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ABSTRACT: Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.European Journal of Human Genetics advance online publication, 13 March 2013; doi:10.1038/ejhg.2013.45.European journal of human genetics: EJHG 03/2013; · 3.56 Impact Factor -
Article: Copy number variation of the antimicrobial-gene, defensin beta 4, is associated with susceptibility to cervical cancer.
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ABSTRACT: The aim of this study was to investigate association between copy number variation of the defensin beta 4 gene (DEFB4) and susceptibility to cervical cancer in a population at high risk of persistent oncogenic human papillomavirus (HPV) infection. The study subjects comprised 204 women with cervical cancer, a population having a high risk of persistent oncogenic HPV infection (cervical cancer group), and 200 healthy women from the general population (control group). Copy number variation of DEFB4 in each test sample was determined by relative quantitation using the comparative CT (ΔΔCT) method. Differences between the two groups were evaluated. The median DEFB4 copy number in the cervical cancer group was four and in the control group was five (P=2.77e-4, t-test). The odds ratio of cervical cancer in individuals with four DEFB4 copies or less was higher (odds ratio 2.02; 95% confidence interval odds ratio 1.36-3.02), compared with that in individuals with five or more copies (odds ratio 0.49; 95% confidence interval odds ratio 0.33-0.74). We found copy number variation of DEFB4 was a host genetic factor conferring susceptibility to cervical cancer. A lower DEFB4 copy number was associated with susceptibility to cervical cancer.Journal of Human Genetics advance online publication, 7 March 2013; doi:10.1038/jhg.2013.7.Journal of Human Genetics 03/2013; · 2.57 Impact Factor -
Article: [Molecular cloning and characterisation of UVSSA, the responsible gene for UV-sensitive syndrome].
Seikagaku. The Journal of Japanese Biochemical Society 03/2013; 85(3):133-44. · 0.04 Impact Factor -
Article: Characterization of placenta-specific microRNAs in fetal growth restriction pregnancy.
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ABSTRACT: OBJECTIVE: The aim of this study was to characterize placenta-specific microRNAs in fetal growth restriction (FGR) pregnancy. METHOD: Placenta-specific miRNAs were identified by next-generation sequencing analysis. Subsequently, quantitative real-time reverse-transcription polymerase chain reaction was used to identify FGR placenta-specific miRNAs whose level of expression was significantly decreased in FGR placenta (n = 45) compared with uncomplicated placenta (n = 50). FGR pregnancy-associated, placenta-specific microRNAs were identified in maternal plasma after delivery at significantly decreased concentrations, and their circulating levels in maternal plasma was compared between FGR pregnancies (n = 10) and uncomplicated pregnancies (n = 10). RESULTS: Out of the ten placenta-specific microRNAs that we identified, seven placenta-specific microRNAs (hsa-miR-518b, hsa-miR-1323, hsa-miR-516b, hsa-miR-515-5p, hsa-miR-520h, hsa-miR-519d, and hsa-miR-526b) from the chromosome 19 microRNA cluster were identified as FGR placenta-specific microRNAs. Four FGR placenta-specific microRNAs (hsa-miR-518b, hsa-miR-1323, hsa-miR-520h, and hsa-miR-519d) were confirmed as FGR pregnancy-associated, placenta-specific miRNAs, but their circulating levels in maternal plasma showed no significant differences between FGR pregnancy and uncomplicated pregnancy. CONCLUSION: Our data suggest that reduced expression in placenta of certain FGR placenta-specific miRNAs is associated with FGR and that the discrepancy between expression in FGR placenta and their circulating levels in maternal plasma will be crucial to understanding how placenta-specific microRNAs are released into the maternal circulation. © 2013 John Wiley & Sons, Ltd.Prenatal Diagnosis 01/2013; · 2.11 Impact Factor
