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Mol Genet Metab. 2016 Sep;119(1-2):8-13. doi: 10.1016/j.ymgme.2016.07.003. Epub 2016 Jul 12.

Epigenotype, genotype, and phenotype analysis of patients in Taiwan with Beckwith-Wiedemann syndrome.

Author information

1
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.
2
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.
3
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
4
Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
5
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
6
Department of Pediatrics, Mackay Memorial Hospital, Hsinchu, Taiwan.
7
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
8
Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
9
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
10
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.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Beckwith–Wiedemann syndrome; Epigenotype; Genotype; Methylation; Phenotype

PMID:
27436784
DOI:
10.1016/j.ymgme.2016.07.003
[Indexed for MEDLINE]

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