Identification of Novel Mutations in ABCA4 Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease.
Stargardt disease (STGD) is the leading cause of juvenile macular degeneration associated with progressive central vision loss, photophobia, and colour vision abnormalities. In this study, we have described the clinical and genetic features of Stargardt patients from an Indian cohort. The next generation sequencing was carried out in five clinically confirmed unrelated patients and their family members using a gene panel comprising 184 retinal specific genes. Sequencing results were analyzed by read mapping and variant calling in genes of interest, followed by their verification and interpretation. Genetic analysis revealed ABCA4 mutations in all of the five unrelated patients. Among these, four patients were found with compound heterozygous mutations and another one had homozygous mutation. All the affected individuals showed signs and symptoms consistent with the disease phenotype. We report two novel ABCA4 mutations in Indian patients with STGD disease, which expands the existing spectrum of disease-causing variants and the understanding of phenotypic and genotypic correlations. Screening for causative mutations in patients with STGD using panel of targeted gene sequencing by NGS would be a cost effective tool, might be helpful in confirming the precise diagnosis, and contributes towards the genetic counselling of asymptomatic carriers and isolated patients.
Department of Vitreoretina, Narayana Nethralaya, Bangalore, India.
Rajani
R
Battu
GROW Research Laboratory, Narayana Nethralaya, Narayana Health City, Bommasandra, Bangalore, Karnataka 560 099, India.
Anshuman
A
Verma
Strand Life Sciences Pvt. Ltd., Bangalore, India.
Ramesh
R
Hariharan
Strand Life Sciences Pvt. Ltd., Bangalore, India.
Shuba
S
Krishna
Strand Life Sciences Pvt. Ltd., Bangalore, India.
Ravi
R
Kiran
Strand Life Sciences Pvt. Ltd., Bangalore, India.
Jemima
J
Jacob
Strand Life Sciences Pvt. Ltd., Bangalore, India.
Aparna
A
Ganapathy
MedGenome Labs Pvt. Ltd., Bangalore, India.
Vedam L
VL
Ramprasad
GROW Research Laboratory, Narayana Nethralaya, Narayana Health City, Bommasandra, Bangalore, Karnataka 560 099, India ; Singapore Eye Research Institute, Singapore.
Govindasamy
G
Kumaramanickavel
GROW Research Laboratory, Narayana Nethralaya, Narayana Health City, Bommasandra, Bangalore, Karnataka 560 099, India.
Nallathambi
N
Jeyabalan
GROW Research Laboratory, Narayana Nethralaya, Narayana Health City, Bommasandra, Bangalore, Karnataka 560 099, India ; Singapore Eye Research Institute, Singapore.
Arkasubhra
A
Ghosh
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D008268:Macular Degeneration / Q000151:congenital* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D000080362:Stargardt Disease
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters