The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis.

Details

Serval ID
serval:BIB_11F7CF94E637
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis.
Journal
Experimental eye research
Author(s)
Dudakova L., Evans C.J., Pontikos N., Hafford-Tear N.J., Malinka F., Skalicka P., Horinek A., Munier F.L., Voide N., Studeny P., Vanikova L., Kubena T., Rojas Lopez K.E., Davidson A.E., Hardcastle A.J., Tuft S.J., Liskova P.
ISSN
1096-0007 (Electronic)
ISSN-L
0014-4835
Publication state
Published
Issued date
05/2019
Peer-reviewed
Oui
Volume
182
Pages
160-166
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The aim of this study was to identify the molecular genetic cause of disease in posterior polymorphous corneal dystrophy (PPCD) probands of diverse origin and to assess the utility of massively parallel sequencing in the detection of ZEB1 mutations. We investigated a total of 12 families (five British, four Czech, one Slovak and two Swiss). Ten novel and two recurrent disease-causing mutations in ZEB1, were identified in probands by Sanger (n = 5), exome (n = 4) and genome (n = 3) sequencing. Sanger sequencing was used to confirm the mutations detected by massively parallel sequencing, and to perform segregation analysis. Genome sequencing revealed that one proband harboured a novel ∼0.34 Mb heterozygous de novo deletion spanning exons 1-7 and part of exon 8. Transcript analysis confirmed that the ZEB1 transcript is detectable in blood-derived RNA samples and that the disease-associated variant c.482-2A>G leads to aberrant pre-mRNA splicing. De novo mutations, which are a feature of PPCD3, were found in the current study with an incidence rate of at least 16.6%. In general, massively parallel sequencing is a time-efficient way to detect PPCD3-associated mutations and, importantly, genome sequencing enables the identification of full or partial heterozygous ZEB1 deletions that can evade detection by both Sanger and exome sequencing. These findings contribute to our understanding of PPCD3, for which currently, 49 pathogenic variants have been identified, all of which are predicted to be null alleles.
Keywords
Adolescent, Adult, Aged, Base Sequence, Child, Child, Preschool, Corneal Dystrophies, Hereditary/diagnosis, Corneal Dystrophies, Hereditary/genetics, Corneal Dystrophies, Hereditary/metabolism, DNA/genetics, DNA Mutational Analysis, Exons, Heterozygote, High-Throughput Nucleotide Sequencing, Humans, Middle Aged, Mutation, Pedigree, Sequence Deletion, Young Adult, Zinc Finger E-box-Binding Homeobox 1/genetics, Zinc Finger E-box-Binding Homeobox 1/metabolism, Zinc Fingers, Aberrant splicing, Breakpoint mapping, Exome, Genome, Massively parallel sequencing, Posterior polymorphous corneal dystrophy type 3, ZEB1
Pubmed
Web of science
Create date
08/04/2019 17:48
Last modification date
21/02/2020 7:19
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