Genetic spectrum of retinal dystrophies in Tunisia.
ATP-Binding Cassette Transporters
/ genetics
Adolescent
Adult
Child
Child, Preschool
Cohort Studies
DNA Mutational Analysis
Eye Proteins
/ genetics
Female
Genetic Testing
/ statistics & numerical data
Humans
Infant
Male
Membrane Proteins
/ genetics
Middle Aged
Mutation
Nerve Tissue Proteins
/ genetics
Pedigree
Phosphotransferases (Alcohol Group Acceptor)
/ genetics
Prevalence
Retinal Dystrophies
/ congenital
Tunisia
/ epidemiology
Exome Sequencing
Young Adult
cis-trans-Isomerases
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
08 07 2020
08 07 2020
Historique:
received:
30
07
2019
accepted:
09
06
2020
entrez:
10
7
2020
pubmed:
10
7
2020
medline:
22
12
2020
Statut:
epublish
Résumé
We report the molecular basis of the largest Tunisian cohort with inherited retinal dystrophies (IRD) reported to date, identify disease-causing pathogenic variants and describe genotype-phenotype correlations. A subset of 26 families from a cohort of 73 families with clinical diagnosis of autosomal recessive IRD (AR-IRD) excluding Usher syndrome was analyzed by whole exome sequencing and autozygosity mapping. Causative pathogenic variants were identified in 50 families (68.4%), 42% of which were novel. The most prevalent pathogenic variants were observed in ABCA4 (14%) and RPE65, CRB1 and CERKL (8% each). 26 variants (8 novel and 18 known) in 19 genes were identified in 26 families (14 missense substitutions, 5 deletions, 4 nonsense pathogenic variants and 3 splice site variants), with further allelic heterogeneity arising from different pathogenic variants in the same gene. The most common phenotype in our cohort is retinitis pigmentosa (23%) and cone rod dystrophy (23%) followed by Leber congenital amaurosis (19.2%). We report the association of new disease phenotypes. This research was carried out in Tunisian patients with IRD in order to delineate the genetic population architecture.
Identifiants
pubmed: 32641690
doi: 10.1038/s41598-020-67792-y
pii: 10.1038/s41598-020-67792-y
pmc: PMC7343876
doi:
Substances chimiques
ABCA4 protein, human
0
ATP-Binding Cassette Transporters
0
CRB1 protein, human
0
Eye Proteins
0
Membrane Proteins
0
Nerve Tissue Proteins
0
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
ceramide kinase
EC 2.7.1.138
retinoid isomerohydrolase
EC 3.1.1.64
cis-trans-Isomerases
EC 5.2.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11199Références
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