Targeted next generation sequencing and family survey enable correct genetic diagnosis in CRX associated macular dystrophy - a case report.
ABCA4 sequence variant, mutation
CRX
Macular dystrophy
Next generation sequencing
Phenotype/genotype, reduced penetrance, family survey
Retina
Journal
BMC ophthalmology
ISSN: 1471-2415
Titre abrégé: BMC Ophthalmol
Pays: England
ID NLM: 100967802
Informations de publication
Date de publication:
09 Apr 2021
09 Apr 2021
Historique:
received:
24
06
2019
accepted:
23
03
2021
entrez:
10
4
2021
pubmed:
11
4
2021
medline:
15
5
2021
Statut:
epublish
Résumé
We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX. A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members. We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis.
Sections du résumé
BACKGROUND
BACKGROUND
We present 3 members of a family with macular dystrophy, originally diagnosed as Stargardt disease, with a significantly variable age at onset, caused by a heterozygous mutation in CRX.
CASE PRESENTATION
METHODS
A 43-year-old female with bull's eye maculopathy, whose sister was diagnosed with Stargardt disease previously at another centre, was found to have a single ABCA4 variant. Further examination of the family revealed that the asymptomatic father was also affected, indicating a dominant pattern of inheritance. In addition, the ABCA4 variant was not identified in the sister originally diagnosed with Stargardt disease. Next generation sequencing identified a heterozygous c.121C > T, p.R41W missense mutation in CRX in all 3 affected members.
CONCLUSIONS
CONCLUSIONS
We describe a common phenotype, but with variable age at onset, with autosomal dominant inheritance and reduced penetrance in a family found to have a pathogenic sequence variant in CRX. This illustrates the importance of panel based molecular genetic testing accompanied by family studies to establish a definitive diagnosis.
Identifiants
pubmed: 33836713
doi: 10.1186/s12886-021-01919-1
pii: 10.1186/s12886-021-01919-1
pmc: PMC8034119
doi:
Substances chimiques
ABCA4 protein, human
0
ATP-Binding Cassette Transporters
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
168Subventions
Organisme : NIHR Clinical Research Network Thames Valley and South Midlands (GB)
ID : NA
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