The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F19%3A10394447" target="_blank" >RIV/00216208:11110/19:10394447 - isvavai.cz</a>
Alternative codes found
RIV/68407700:21230/19:00330094 RIV/00216208:11120/19:43917763 RIV/00064173:_____/19:N0000145 RIV/00064165:_____/19:10394447
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=9KpyePh.f4" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=9KpyePh.f4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.exer.2019.03.002" target="_blank" >10.1016/j.exer.2019.03.002</a>
Alternative languages
Result language
angličtina
Original language name
The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis
Original language description
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 TILDE OPERATOR+D910.34 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30207 - Ophthalmology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Experimental Eye Research
ISSN
0014-4835
e-ISSN
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Volume of the periodical
182
Issue of the periodical within the volume
May
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
160-166
UT code for WoS article
000468258300018
EID of the result in the Scopus database
2-s2.0-85063726886