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 gene encodes the kinesin-like protein Kif17, a microtubule...

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Published in:International journal of molecular sciences 2021-04, Vol.22 (9), p.4471
Main Authors: 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
Format: Article
Language:English
Subjects:
Abnormalities
Animal models
Anomalies
Anophthalmia
Binding sites
Birth weight
Births
Cesarean section
Cognitive development
coloboma
Congenital diseases
congenital eye defects
Deoxyribonucleic acid
DNA
Electrocardiography
Eye
Eye (anatomy)
Gene expression
Genomes
Genomics
KIF17
Kinesin
Laboratories
MAC spectrum
Microphthalmia
Molecular motors
Morphogenesis
Nucleotide sequence
Optic nerve
Phenotypes
Proteins
Siblings
Zebrafish
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Summary: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 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 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 variants with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development across different species.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22094471