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Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum

Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called “MAC spectrum”. The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-bas...

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Autores principales: Riva, Antonella, Gambadauro, Antonella, Dipasquale, Valeria, Casto, Celeste, Ceravolo, Maria Domenica, Accogli, Andrea, Scala, Marcello, Ceravolo, Giorgia, Iacomino, Michele, Zara, Federico, Striano, Pasquale, Cuppari, Caterina, Di Rosa, Gabriella, Cutrupi, Maria Concetta, Salpietro, Vincenzo, Chimenz, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123208/
https://www.ncbi.nlm.nih.gov/pubmed/33922911
http://dx.doi.org/10.3390/ijms22094471
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author Riva, Antonella
Gambadauro, Antonella
Dipasquale, Valeria
Casto, Celeste
Ceravolo, Maria Domenica
Accogli, Andrea
Scala, Marcello
Ceravolo, Giorgia
Iacomino, Michele
Zara, Federico
Striano, Pasquale
Cuppari, Caterina
Di Rosa, Gabriella
Cutrupi, Maria Concetta
Salpietro, Vincenzo
Chimenz, Roberto
author_facet Riva, Antonella
Gambadauro, Antonella
Dipasquale, Valeria
Casto, Celeste
Ceravolo, Maria Domenica
Accogli, Andrea
Scala, Marcello
Ceravolo, Giorgia
Iacomino, Michele
Zara, Federico
Striano, Pasquale
Cuppari, Caterina
Di Rosa, Gabriella
Cutrupi, Maria Concetta
Salpietro, Vincenzo
Chimenz, Roberto
author_sort Riva, Antonella
collection PubMed
description Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called “MAC spectrum”. The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-based, ATP-dependent, motor protein that is pivotal for outer segment development and disc morphogenesis in different animal models, including mice and zebrafish. In this report, we describe a Sicilian family with two siblings affected with congenital coloboma, microphthalmia, and a mild delay of motor developmental milestones. Genomic DNA from the siblings and their unaffected parents was sequenced with a clinical exome that revealed compound heterozygous variants in the KIF17 gene (NM_020816.4: c.1255C > T (p.Arg419Trp); c.2554C > T (p.Arg852Cys)) segregating with the MAC spectrum phenotype of the two affected siblings. Variants were inherited from the healthy mother and father, are present at a very low-frequency in genomic population databases, and are predicted to be deleterious in silico. Our report indicates the potential co-segregation of these biallelic KIF17 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species.
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spelling pubmed-81232082021-05-16 Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum Riva, Antonella Gambadauro, Antonella Dipasquale, Valeria Casto, Celeste Ceravolo, Maria Domenica Accogli, Andrea Scala, Marcello Ceravolo, Giorgia Iacomino, Michele Zara, Federico Striano, Pasquale Cuppari, Caterina Di Rosa, Gabriella Cutrupi, Maria Concetta Salpietro, Vincenzo Chimenz, Roberto Int J Mol Sci Article Microphthalmia, anophthalmia, and coloboma (MAC) are a group of congenital eye anomalies that can affect one or both eyes. Patients can present one or a combination of these ocular abnormalities in the so called “MAC spectrum”. The KIF17 gene encodes the kinesin-like protein Kif17, a microtubule-based, ATP-dependent, motor protein that is pivotal for outer segment development and disc morphogenesis in different animal models, including mice and zebrafish. In this report, we describe a Sicilian family with two siblings affected with congenital coloboma, microphthalmia, and a mild delay of motor developmental milestones. Genomic DNA from the siblings and their unaffected parents was sequenced with a clinical exome that revealed compound heterozygous variants in the KIF17 gene (NM_020816.4: c.1255C > T (p.Arg419Trp); c.2554C > T (p.Arg852Cys)) segregating with the MAC spectrum phenotype of the two affected siblings. Variants were inherited from the healthy mother and father, are present at a very low-frequency in genomic population databases, and are predicted to be deleterious in silico. Our report indicates the potential co-segregation of these biallelic KIF17 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species. MDPI 2021-04-25 /pmc/articles/PMC8123208/ /pubmed/33922911 http://dx.doi.org/10.3390/ijms22094471 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Riva, Antonella
Gambadauro, Antonella
Dipasquale, Valeria
Casto, Celeste
Ceravolo, Maria Domenica
Accogli, Andrea
Scala, Marcello
Ceravolo, Giorgia
Iacomino, Michele
Zara, Federico
Striano, Pasquale
Cuppari, Caterina
Di Rosa, Gabriella
Cutrupi, Maria Concetta
Salpietro, Vincenzo
Chimenz, Roberto
Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum
title Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum
title_full Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum
title_fullStr Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum
title_full_unstemmed Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum
title_short Biallelic Variants in KIF17 Associated with Microphthalmia and Coloboma Spectrum
title_sort biallelic variants in kif17 associated with microphthalmia and coloboma spectrum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123208/
https://www.ncbi.nlm.nih.gov/pubmed/33922911
http://dx.doi.org/10.3390/ijms22094471
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