Abstract
BackgroundStargardt disease 1 (STGD1; MIM 248200) is a monogenic form of autosomal recessive genetic disease caused by mutation in ABCA4. This gene has a major role in hydrolyzing N-retinylidene-phosphatidylethanolamine to all-trans-retinal and phosphatidylethanolamine. The purpose of this study is to identify the frequency of putative disease-causing mutations associated with Stargardt disease in a South Indian population.MethodsA total of 28 clinically diagnosed Stargardt-like phenotype patients were recruited from south India. Ophthalmic examination of all patients was carefully carried out by a retina specialist based on the stages of fundus imaging and ERG grouping. Genetic analysis of ABCA4 was performed for all patients using Sanger sequencing and clinical exome sequencing.ResultsThis study identified disease-causing mutations in ABCA4 in 75% (21/28) of patients, 7% (2/28) exhibited benign variants and 18% (5/28) were negative for the disease-causing mutation.ConclusionThis is the first study describing the genetic association of ABCA4 disease-causing mutation in South Indian Stargardt 1 patients (STGD1). Our findings highlighted the presence of two novel missense mutations and an (in/del, single base pair deletion & splice variant) in ABCA4. However, genetic heterogeneity in ABCA4 mutants requires a larger sample size to establish a true correlation with clinical phenotype.
Highlights
Stargardt disease 1 (STGD1; MIM 248200) is a monogenic form of autosomal recessive genetic disease caused by mutation in ATP Binding Cassette Subfamily A Member 4 (ABCA4)
The disease progression of STGD1 based on fundus imaging (Fishman’s classification) [23] and ERG grouping [24] (Fig. 1) was keenly categorized by our clinicians
Of the total 11 probands, 27% were diagnosed with stage-1 disease, 36% were categorized as in STGD1 cases (IDs) Age/Sex Age of onset Best corrected visual acuity (BCVA) in BE Fundus
Summary
Stargardt disease 1 (STGD1; MIM 248200) is a monogenic form of autosomal recessive genetic disease caused by mutation in ABCA4 This gene has a major role in hydrolyzing N-retinylidene-phosphatidylethanolamine to all-trans-retinal and phosphatidylethanolamine. The globally estimated prevalence rate is 1 in 8000–10,000 It is characterized by early central vision loss, progressive degeneration of the macula that is associated with loss of photoreceptors leading to irreversible vision loss [3, 4]. The ABCA4 gene located in chromosome 1p22.1 contains 50 exons that codes for a membrane bound glycoprotein that is ubiquitous and localized to the rim of the rod and cone outer discs membrane [9] It is actively involved in the transport of retinoid substrate (2020) 7:3 from photoreceptor to RPE [10]. Only one study reported the clinical and genetic correlation of STGD1 disease in five families belonging to of Indian origin [12]
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