title: Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome.
abstract: Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder predisposing to tumorigenesis that results from abnormal expression or function of imprinted genes of chromosome 11p15.5.
  
  
  
  Forty-seven patients in Taiwan with clinical suspicion of BWS were referred for diagnostic testing based on methylation profiling of H19-associated imprinting center (IC) 1 and KCNQ1OT1-associated IC2 using high-resolution melting analysis, multiplex ligation-dependent probe amplification, or high-resolution quantitative methylation profiling.
  
  
  
  Twenty-eight patients received a clinical diagnosis of BWS (the presence of 3 major features or 2 major features and at least 1 minor feature), 18 had suspected BWS (the presence of at least 1 major feature), and 1 had isolated Wilms' tumor. Nineteen patients were identified with IC2 hypomethylation (including 1 with isolated Wilms' tumor), 1 with IC1 hypermethylation, 2 with paternal uniparental disomy, and 1 with CDKN1C mutation. Several clinical features were found to be statistically different (P<0.05) between the 2 groups-clinical diagnosis of BWS (n=28) or suspected BWS (n=18)-including macroglossia, pre- or postnatal gigantism, abdominal wall defect, ear creases, facial nevus flammeus, BWS score, and the molecular diagnosis rate. Molecular lesion was detected in 81% of patients with the presence of three major features, compared with 33% and 28% of those with two or one major feature, respectively. The mean BWS score was 5.6 for 19 subjects with "IC2 hypomethylation", compared with 3.8 for 2 subjects with pUPD. The BWS score of one subject with CDKN1C mutation and one with IC1 hypermethylation was 6 and 7, respectively.
  
  
  
  The BWS score was positively correlated with the molecular diagnosis rate (P<0.01). The BWS database of epigenotype, genotype, and phenotype is expected to promote better genetic counseling and medical care of these patients.
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsiang-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Medical College, Fu-Jen Catholic University, Taipei, Taiwan; Institute of Biotechnology, National Taipei University of Technology, Taipei, Taiwan.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chuang
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Ru-Yi
authors.initials: RY
authors.lastname: Tu
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yi-Ya
authors.initials: YY
authors.lastname: Fang
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Chih-Ping
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Hsi-Che
authors.initials: HC
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Chu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Dau-Ming
authors.initials: DM
authors.lastname: Niu
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan. Electronic address: 4535lin@gmail.com.
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics*; D055815:Young Adult
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C094335:H19 long non-coding RNA; C449939:KCNQ1OT1 RNA; D062085:RNA, Long Noncoding
keywords: Beckwith–Wiedemann syndrome; Epigenotype; Genotype; Methylation; Phenotype