A novel MERTK mutation causing retinitis pigmentosa.
Graefes Arch Clin Exp Ophthalmol
; 255(8): 1613-1619, 2017 Aug.
Article
em En
| MEDLINE
| ID: mdl-28462455
ABSTRACT
PURPOSE:
Retinitis pigmentosa (RP) is a genetically heterogeneous inherited retinal dystrophy. To date, over 80 genes have been implicated in RP. However, the disease demonstrates significant locus and allelic heterogeneity not entirely captured by current testing platforms. The purpose of the present study was to characterize the underlying mutation in a patient with RP without a molecular diagnosis after initial genetic testing.METHODS:
Whole-exome sequencing of the affected proband was performed. Candidate gene mutations were selected based on adherence to expected genetic inheritance pattern and predicted pathogenicity. Sanger sequencing of MERTK was completed on the patient's unaffected mother, affected brother, and unaffected sister to determine genetic phase.RESULTS:
Eight sequence variants were identified in the proband in known RP-associated genes. Sequence analysis revealed that the proband was a compound heterozygote with two independent mutations in MERTK, a novel nonsense mutation (c.2179C > T) and a previously reported missense variant (c.2530C > T). The proband's affected brother also had both mutations. Predicted phase was confirmed in unaffected family members.CONCLUSION:
Our study identifies a novel nonsense mutation in MERTK in a family with RP and no prior molecular diagnosis. The present study also demonstrates the clinical value of exome sequencing in determining the genetic basis of Mendelian diseases when standard genetic testing is unsuccessful.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Retinose Pigmentar
/
C-Mer Tirosina Quinase
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Graefes Arch Clin Exp Ophthalmol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos