Non-Penetrance for Ocular Phenotype in Two Individuals Carrying Heterozygous Loss-of-Function ZEB1 Alleles

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10429153" target="_blank" >RIV/00216208:11110/21:10429153 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/21:10429153

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OD1I19VIpm" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=OD1I19VIpm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/genes12050677" target="_blank" >10.3390/genes12050677</a>

Result language

angličtina

Original language name

Non-Penetrance for Ocular Phenotype in Two Individuals Carrying Heterozygous Loss-of-Function ZEB1 Alleles

Original language description

ZEB1 loss-of-function (LoF) alleles are known to cause a rare autosomal dominant disorder-posterior polymorphous corneal dystrophy type 3 (PPCD3). To date, 50 pathogenic LoF variants have been identified as disease-causing and familial studies have indicated that the PPCD3 phenotype is penetrant in approximately 95% of carriers. In this study, we interrogated in-house exomes (n = 3616) and genomes (n = 88) for the presence of putative heterozygous LoF variants in ZEB1. Next, we performed detailed phenotyping in a father and his son who carried a novel LoF c.1279C&gt;T; p.(Glu427*) variant in ZEB1 (NM_030751.6) absent from the gnomAD v.2.1.1 dataset. Ocular examination of the two subjects did not show any abnormalities characteristic of PPCD3. GnomAD (n = 141,456 subjects) was also interrogated for LoF ZEB1 variants, notably 8 distinct heterozygous changes presumed to lead to ZEB1 haploinsufficiency, not reported to be associated with PPCD3, have been identified. The NM_030751.6 transcript has a pLI score &gt;= 0.99, indicating extreme intolerance to haploinsufficiency. In conclusion, ZEB1 LoF variants are present in a general population at an extremely low frequency. As PPCD3 can be asymptomatic, the true penetrance of ZEB1 LoF variants remains currently unknown but is likely to be lower than estimated by the familial led approaches adopted to date.

Czech name

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Czech description

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Type

J_imp - 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

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)

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Genes

ISSN

2073-4425

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

5

Country of publishing house

CH - SWITZERLAND

Number of pages

8

Pages from-to

677

UT code for WoS article

000653949200001

EID of the result in the Scopus database

2-s2.0-85105479744