Identification of Novel Mutations inABCA4Gene: Clinical and Genetic Analysis of Indian Patients with Stargardt Disease

Abstract

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.

Stargardt disease-associated mutation spectrum of a Russian Federation cohort

“…This mutation is previously reported in Russian and Indian(Battu et al 2015) STGD1 patients and in several European populations, including British, Spanish(Paloma et al 2001), Portuguese (Maia-Lopes et al 2009), Danish, Italian, and German) STGD1 cohorts.…”

“…Although genetic variations associated with STGD1 and other ABCA4-related retinopathies are reported for Chinese (Zhou et al 2014), British , Japanese (Fukui et al 2002), Indian (Battu et al 2015), German (Rivera et al 2000), Spanish (Paloma et al 2001), Hungarian (Hargitai et al 2005), Portuguese ), Danish , Italian , Turkish (Ozgul et al 2004), Mexican (Chacon-Camacho et al 2013),…”

Spectrum of Molecular Genetic Alterations and Diversity of Clinical Forms of Stargardt Disease

“…В таких случаях изначальная БШ может прогрессировать с течением времени в тяжелую распространенную дегенерацию, диагностируемую как ПКД [6,9,18]. Более позднее начало заболевания отмечено при мягких/умеренных мутациях и ассоциировано в большинстве случаев с локальными поражениями сетчатки [4,7]. Поздний дебют, по данным нашего исследования, был замечен преимущественно у пациентов с мутацией p.G1961E.…”

Application of targeted exome and whole‐exome sequencing for Chinese families with Stargardt disease

“…It may lead to atrophy of the macular retinal pigment epithelium and loss of photoreceptors. The remaining three genes are responsible for autosomal-dominant STGD (Battu et al, 2015;Logan et al, 2013;Yi et al, 2012). Variants in the ABCA4 gene cause autosomal recessive STGD, which is responsible for disease in >95% of STGD patients (Haji Abdollahi & Hirose, 2013).…”

“…Variants in the ABCA4 gene cause autosomal recessive STGD, which is responsible for disease in >95% of STGD patients (Haji Abdollahi & Hirose, 2013). The remaining three genes are responsible for autosomal-dominant STGD (Battu et al, 2015;Logan et al, 2013;Yi et al, 2012). Thus far, 1,283 disease-associated ABCA4 variants have been identified (http://www.hgmd.cf.ac.uk/ac/index.php, updated 2019.1).…”