HOMOZYGOSITY FOR A NOVEL DOUBLE MUTANT ALLELE (G1961E/L857P) UNDERLIES CHILDHOOD-ONSET ABCA4-RELATED RETINOPATHY IN THE UNITED ARAB EMIRATES.
Retina
; 40(7): 1429-1433, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-31318848
ABSTRACT
PURPOSE:
Stargardt disease (On-Line Mendelian Inheritance In Man 242000, STGD1) is the most common inherited macular dystrophy. STGD1 is typically a young-adult-onset disease that is recurrently associated with the ABCA4 mutant allele G1961E in homozygosity or compound heterozygosity. The genetics of ABCA4-related retinopathy in the Arabian Gulf region have not been well-studied. This report reviews the experience of the Ocular Genetics Service at Cleveland Clinic Abu Dhabi with clinically diagnosed ABCA4-related retinopathy in Emirati patients who underwent genetic testing.METHODS:
Retrospective case series (2016-2018, inclusive).RESULTS:
All 22 identified patients (19 families; 11 males, 11 females; first visual symptoms 5-33 years old) were found to harbor biallelic ABCA4 pathologic variants. There were 14 childhood-onset cases (onset before 18 years of age; 12 families; 7 males, 7 females; first visual symptoms from 5 to 12 years old, median 8)-all were homozygous, 11 for the same novel double mutant allele G1961E/L857P. Those who underwent electroretinography (8) had cone-rod rather than isolated macular dystrophy. There were 8 adult-onset cases (onset at or after 18 years of age; 7 families; 4 males, 4 females; first visual symptoms from 18 to 33 years old, median 22)-all were compound heterozygous, seven harboring the common G1961E mutant allele.CONCLUSION:
The molecular yield for biallelic ABCA4 pathogenic variants is high for clinically diagnosed ABCA4-related retinopathy in Emiratis (100% in this case series). Homozygosity for a novel complex allele G1961E/L857P causes a childhood-onset cone-rod dystrophy rather than the young-adult-onset macular dystrophy that is associated with G1961E alone. This G1961/L857P complex allele likely represents a founder effect for the region.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Acuidade Visual
/
Transportadores de Cassetes de Ligação de ATP
/
Doença de Stargardt
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Child
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Child, preschool
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article