Screening of<i>ABCA4</i>Gene in a Chinese Cohort With Stargardt Disease or Cone-Rod Dystrophy With a Report on 85 Novel Mutations

Jiang, Feng; Pan, Zhe; Xu, Ke; Tian, Lu; Xie, Yue; Zhang, Xiaohui; Chen, Jieqiong; Dong, Bing; Li, Yang

doi:10.1167/iovs.15-18190

Cited by 54 publications

(59 citation statements)

References 35 publications

(66 reference statements)

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“…At that time targeted NGS and whole exome sequencing (WES) was not available in our laboratory. The rate of bi-allelic variants detected in the population using this approach was 75.6%, which is in accordance with previously reported data (about 75%) [15,16,17,18,19]. …”

Section: Discussionsupporting

confidence: 92%

“…Nevertheless, homozygous or compound heterozygous mutations are regularly detected in no more than 70–75% of STGD1 patients, while a significant number of patients carry only a single ABCA4 mutation or none at all [15,16,17,18,19]. On the other hand, several deep intronic variants in non-coding regions were reported to segregate with STGD1 affecting correct splicing mechanisms [19,20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

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Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

Nassisi

Mohand‐Saïd

Dhaenens

et al. 2018

IJMS

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Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and direct Sanger sequencing. At the end of the screening, at least two likely pathogenic mutations were found in 302 patients (76.1%) while 95 remained unsolved: 40 (10.1%) with no variants identified, 52 (13.1%) with one heterozygous mutation, and 3 (0.7%) with at least one variant of uncertain significance (VUS). Sixty-three novel variants were identified in the cohort. Three of them were variants of uncertain significance. The other 60 mutations were classified as likely pathogenic or pathogenic, and were identified in 61 patients (15.4%). The majority of those were missense (55%) followed by frameshift and nonsense (30%), intronic (11.7%) variants, and in-frame deletions (3.3%). Only patients with variants never reported in literature were further analyzed herein. Recruited subjects underwent complete ophthalmic examination including best corrected visual acuity, kinetic and static perimetry, color vision test, full-field and multifocal electroretinography, color fundus photography, short-wavelength and near-infrared fundus autofluorescence imaging, and spectral domain optical coherence tomography. Clinical evaluation of each subject confirms the tendency that truncating mutations lead to a more severe phenotype with electroretinogram (ERG) impairment (p = 0.002) and an earlier age of onset (p = 0.037). Our study further expands the mutation spectrum in the exonic and flanking regions of ABCA4 underlying Stargardt disease.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

Nassisi

Mohand‐Saïd

Dhaenens

et al. 2018

IJMS

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“…The percentage of patients who had deleterious mutations was higher in the early disease onset group (< 10 years of age; 66.7%, 4/6), which implies that alleles expressing nonfunctional proteins result in more severe clinical manifestations, consistent with the results of previous studies [27,28]. These patients tended to have an early onset age and relatively poor VA. VA was significantly lower in patients whose disease occurred at 10-20 years of age, and also significantly and positively correlated with the age at onset.…”

Section: Discussionsupporting

confidence: 86%

Clinical and Genetic Characteristics Analysis of Korean Patients with Stargardt Disease Using Targeted Exome Sequencing

et al. 2018

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Purpose: To investigate genetic mutations in Korean patients with Stargardt disease (STGD) using exome sequencing, and to analyze the correlations between genetic mutations and clinical phenotypes. Methods: Peripheral venous blood was obtained from 24 clinically diagnosed Korean STGD patients, followed by extraction of genomic DNAs. Using exome sequencing we investigated gene mutations for the adenosine triphosphate-binding cassette, subfamily A, member 4 (ABCA4) elongation of very-long-chain fatty acids 4 (ELOVL4), and prominin 1 (PROM1), and confirmed gene mutations by the direct sequencing of polymerase chain reaction products. Results: ABCA4 mutations were confirmed in 17 of 24 patients, and 12 novel mutations were identified. ELOVL4 and PROM1 gene mutations were not identified in this study. We also identified 16 previously reported mutations related to STGD1. In patients whose disease symptoms occurred before 20 years of age, visual acuity was poorer and atrophic flecks were more frequently found. In addition, more ABCA4 mutations were found in patients who had choroidal silence or atrophic flecks. Conclusions: Novel ABCA4 gene mutations were found in Korean patients with STGD1. This study will facilitate better understanding of the relationships between ABCA4 gene mutations and clinical symptoms in Korean patients.

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“…In patients with STGD, the intronic ABCA4 variant c.5461-10T>C in intron 38 (reference sequence: NM_000350.2), first observed in 1999 (Maugeri et al 1999), has been described as the third most frequent gene variant associated with STGD in individuals with European or African descent (Zernant et al 2011;Roberts et al 2012;Miraldi Utz et al 2014). Interestingly, the variant has not been observed in Chinese patients with STGD or cone-rod dystrophy (Jiang et al 2016). Conflicting results have been reported regarding the effect of this variant on splicing (Rivera et al 2000;Sangermano et al 2016).…”

Section: Introductionmentioning

confidence: 97%

“…Interestingly, the variant has not been observed in Chinese patients with STGD or cone–rod dystrophy (Jiang et al. ). Conflicting results have been reported regarding the effect of this variant on splicing (Rivera et al.…”

Section: Introductionmentioning

confidence: 99%

The intronic ABCA4 c.5461‐10T>C variant, frequently seen in patients with Stargardt disease, causes splice defects and reduced ABCA4 protein level

Aukrust

Jansson

Bredrup

et al. 2016

Acta Ophthalmologica

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Screening ofABCA4Gene in a Chinese Cohort With Stargardt Disease or Cone-Rod Dystrophy With a Report on 85 Novel Mutations

Abstract: The mutation spectrum of the ABCA4 gene in Chinese patients is quite different from that for Caucasian patients. The establishment of the mutation profile will facilitate ABCA4 screening and risk evaluation for Chinese patients with STGD1.

Cited by 54 publications

References 35 publications

Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort

Clinical and Genetic Characteristics Analysis of Korean Patients with Stargardt Disease Using Targeted Exome Sequencing

The intronic ABCA4 c.5461‐10T>C variant, frequently seen in patients with Stargardt disease, causes splice defects and reduced ABCA4 protein level

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