PUBLICATION
A Novel De Novo Missense Variant in Netrin-1 (NTN1) Associated With Chorioretinal Coloboma, Sensorineural Hearing Loss and Polydactyly
- Authors
- Toms, M., Heppell, C., Owen, N., Malka, S., Moosajee, M., Genomics England Research Consortium
- ID
- ZDB-PUB-241209-1
- Date
- 2024
- Source
- Clinical genetics : (Journal)
- Registered Authors
- Keywords
- coloboma, microphthalmia, netrin‐1, polydactyly, sensorineural hearing loss
- MeSH Terms
-
- Animals
- Microphthalmos/genetics
- Microphthalmos/pathology
- Netrin-1*/genetics
- Male
- Female
- Humans
- Phenotype
- Hearing Loss, Sensorineural*/genetics
- Hearing Loss, Sensorineural*/pathology
- Zebrafish*/genetics
- Polydactyly*/genetics
- Coloboma*/genetics
- Coloboma*/pathology
- Mutation, Missense*/genetics
- PubMed
- 39648562 Full text @ Clin. Genet.
Citation
Toms, M., Heppell, C., Owen, N., Malka, S., Moosajee, M., Genomics England Research Consortium (2024) A Novel De Novo Missense Variant in Netrin-1 (NTN1) Associated With Chorioretinal Coloboma, Sensorineural Hearing Loss and Polydactyly. Clinical genetics. :.
Abstract
Microphthalmia, anophthalmia and coloboma (MAC) comprise a highly heterogeneous spectrum of congenital ocular malformations with an estimated incidence of 1 in 5000 to 1 in 30 000 live births. Although there is likely to be a genetic component in the majority of cases, many remain without a molecular diagnosis. Netrin-1 was previously identified as a mediator of optic fissure closure from transcriptome analyses of chick and zebrafish and was shown to cause ocular coloboma when knocked out in both mouse and zebrafish. Here, we report the first patient with chorioretinal coloboma and microphthalmia harbouring a novel heterozygous likely pathogenic NTN1 missense variant, c.1483T>A p.(Tyr495Asn), validating a conserved gene function in ocular development. In addition, the patient displayed bilateral sensorineural hearing loss which was investigated by examining the sensory hair cells of ntn1a morphant zebrafish, suggesting a role for netrin-1 in hair cell development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping