The utility of massively parallel sequencing for posterior polymorphous corneal dystrophy type 3 molecular diagnosis
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30851240
DOI
10.1016/j.exer.2019.03.002
PII: S0014-4835(18)30789-9
Knihovny.cz E-zdroje
- Klíčová slova
- Aberrant splicing, Breakpoint mapping, Exome, Genome, Massively parallel sequencing, Posterior polymorphous corneal dystrophy type 3, ZEB1,
- MeSH
- dědičné dystrofie rohovky diagnóza genetika metabolismus MeSH
- dítě MeSH
- DNA genetika MeSH
- dospělí MeSH
- exony MeSH
- heterozygot MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- předškolní dítě MeSH
- rodokmen MeSH
- sekvence nukleotidů MeSH
- sekvenční delece MeSH
- senioři MeSH
- transkripční faktor Zeb1 genetika metabolismus MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- zinkové prsty MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- transkripční faktor Zeb1 MeSH
- ZEB1 protein, human MeSH Prohlížeč
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.
Center for Eye Microsurgery Gagarinova 7 B 821 03 Bratislava Slovakia
Moorfields Eye Hospital 162 City Road EC1V 2PD London United Kingdom
Ophthalmology Clinic of Dr Tomas Kubena U Zimniho Stadionu 1759 760 00 Zlin Czech Republic
UCL Institute of Ophthalmology 11 43 Bath Street EC1V 9EL London United Kingdom
Citace poskytuje Crossref.org
CUGC for posterior polymorphous corneal dystrophy (PPCD)
