A duplication on chromosome 16q12 affecting the IRXB gene cluster is associated with autosomal dominant cone dystrophy with early tritanopic color vision defect.
Animals
Chromosome Duplication
Chromosomes, Human, Pair 16
/ genetics
Color Vision Defects
/ genetics
Comparative Genomic Hybridization
/ methods
Cone Dystrophy
/ genetics
Family Health
Female
Gene Expression Regulation
Genes, Dominant
/ genetics
Homeodomain Proteins
/ genetics
Humans
Male
Multigene Family
Pedigree
Sequence Analysis, DNA
/ methods
Transcription Factors
/ genetics
Zebrafish
/ genetics
Journal
Human molecular genetics
ISSN: 1460-2083
Titre abrégé: Hum Mol Genet
Pays: England
ID NLM: 9208958
Informations de publication
Date de publication:
17 06 2021
17 06 2021
Historique:
received:
04
02
2021
revised:
15
04
2021
accepted:
15
04
2021
pubmed:
24
4
2021
medline:
29
3
2022
entrez:
23
4
2021
Statut:
ppublish
Résumé
Cone dystrophies are a rare subgroup of inherited retinal dystrophies and hallmarked by color vision defects, low or decreasing visual acuity and central vision loss, nystagmus and photophobia. Applying genome-wide linkage analysis and array comparative genome hybridization, we identified a locus for autosomal dominant cone dystrophy on chromosome 16q12 in four independent multigeneration families. The locus is defined by duplications of variable size with a smallest region of overlap of 608 kb affecting the IRXB gene cluster and encompasses the genes IRX5 and IRX6. IRX5 and IRX6 belong to the Iroquois (Iro) protein family of homeodomain-containing transcription factors involved in patterning and regionalization of embryonic tissue in vertebrates, including the eye and the retina. All patients presented with a unique progressive cone dystrophy phenotype hallmarked by early tritanopic color vision defects. We propose that the disease underlies a misregulation of the IRXB gene cluster on chromosome 16q12 and demonstrate that overexpression of Irx5a and Irx6a, the two orthologous genes in zebrafish, results in visual impairment in 5-day-old zebrafish larvae.
Identifiants
pubmed: 33891002
pii: 6246147
doi: 10.1093/hmg/ddab117
pmc: PMC8212766
doi:
Substances chimiques
Homeodomain Proteins
0
IRX5 protein, human
0
IRX6 protein, human
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1218-1229Informations de copyright
© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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