Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Multiplex Ligation-dependent Probe Amplification Analysis Subsequent to Direct DNA Full Sequencing for Identifying Identifying ATP7B Mutations and Phenotype Correlations in Children with Wilson Disease

Authors
Shim, Jung OkYang, Hye RanMoon, Jin SooChang, Ju YoungKo, Jae SungPark, Sung SupSeo, Jeong Kee
Issue Date
25-6월-2018
Publisher
KOREAN ACAD MEDICAL SCIENCES
Keywords
Wilson Disease; Mutation; Multiplex Ligation-dependent Probe Amplification; Sequence Analysis; Child
Citation
JOURNAL OF KOREAN MEDICAL SCIENCE, v.33, no.26
Indexed
SCIE
SCOPUS
KCI
Journal Title
JOURNAL OF KOREAN MEDICAL SCIENCE
Volume
33
Number
26
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/74896
DOI
10.3346/jkms.2018.33.e177
ISSN
1011-8934
Abstract
Background: Mutations in ATP7B cause Wilson disease (WD). However, direct DNA full sequencing cannot detect all mutations in patients with WD. Multiplex ligation-dependent probe amplification (MLPA) analysis is reportedly useful in increasing the diagnostic yield in other genetic disorders with large deletions or insertions. The aim of this study was to evaluate whether the detection rate of ATP7B mutations can be increased by using MLPA. Methods: We enrolled 114 children with WD from 104 unrelated families based on biochemical tests and direct DNA full sequencing. The patients with one or zero mutant allele were investigated using MLPA. We analyzed phenotypic correlations. Results: Total allele frequency by full sequencing was 87.5%. Full sequencing revealed two mutant alleles in 80 of 104 unrelated children. One mutant allele was detected in 22 children, and no mutations were found in two children. Novel mutations including small deletions with frameshift mutations were identified by DNA sequencing. MLPA revealed no gross deletion or duplication in 24 children with one or zero mutant alleles. The number of detected mutations was not associated with hepatic manifestation, age of onset, Kayser-Fleischer ring, ceruloplasmin, and urinary Cu concentrations. Conclusion: MLPA showed a limited role to increase the mutation detection rate in children who do not receive a definite genetic diagnosis of WD through DNA full sequencing. This finding suggests that large deletions or duplications might be extremely rare in WD. Further development is needed to improve the genetic diagnosis of WD.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Medicine > Department of Medical Science > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Altmetrics

Total Views & Downloads

BROWSE