Identification of a Novel Splicing Mutation in the <i>ARSA</i> Gene in a Patient with Late-infantile Form of Metachromatic Leukodystrophy

Kang, Dong-Hee; Lee, Dong Hwan; Hong, Yong Hee; Lee, Seung Tae; Jeon, Byung Ryul; Lee, You Kyoung; Ki, Chang‐Seok

doi:10.3343/kjlm.2010.30.5.516

Cited by 12 publications

(8 citation statements)

References 10 publications

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“…The incidence of MLD is probably around 1/100,000 live births in the European population (The Netherlands) . In the Korean population, several cases of MLD have been reported but the incidence is not yet known . MLD is classified into three or four clinical subtypes based on the age at onset.…”

mentioning

confidence: 99%

Ultra-performance liquid chromatography/tandem mass spectrometry for determination of sulfatides in dried blood spots from patients with metachromatic leukodystrophy

Han

Jun

Song

et al. 2014

Rapid Commun. Mass Spectrom.

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mentioning

confidence: 99%

Ultra-performance liquid chromatography/tandem mass spectrometry for determination of sulfatides in dried blood spots from patients with metachromatic leukodystrophy

Han

Jun

Song

et al. 2014

Rapid Commun. Mass Spectrom.

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“…Nonsense variants were found also in other studies [17][18][19] and so are splicing defects. 15,20 Missense variants causing MLC1were previously reported in many studies. 21 Judging from the in silico prediction methods which include conservation, allele frequency and tolerance of amino acid changes, our variants reported in our study are very likely to be pathogenic, but they are all novel and their association with these types of leukodystrophies await to be confirmed.…”

Section: Discussionmentioning

confidence: 95%

Untitled

2018

IJMBOA

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Megalencephalic Leukodystrophy with sub cortical cysts is a type of Demyelinating Leukodystrophy caused by mutations in MLC1 gene. Various mutations in MLC1 gene have been reported worldwide but high throughput technologies aimed to discover novel variants underlying this disorder are scarce and there is a lot yet to be discovered. In silico analysis of SNPs in a gene known to cause a disease is a well effective and economic method of analyzing known variants deposited in public databases. This article aimed to analyze all SNPs in MLC1 gene in order to be used in screening programs for patients with Megalencephalic Leukodystrophy. The SNPs in MLC1 gene were retrieved from NCBI db SNP. Variants in VCF format were analyzed using Variant Effect Predictor (VEP) of the Ensemble database. The deleterious coding ns SNPs were detected by the web program SIFT, PolyPhen and Mutation Taster in addition to allele frequency and conservation score. The 3-D model of the human MLC1 protein was predicted using the CPH models 2.0 server. The resulting modeled structure with positions of mutations was viewed using Chimera 1.8 software. In MLC1 gene, 4 are nonsense, 18 are indels (frame shift mutations) and 10 potentially disrupt splicing. Six variants in MLC1 gene were predicted to be pathogenic using the same tools. The results of our study will facilitate future studies aimed to analyze the genetics of Leukodystrophy patients from different families from different populations

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“…Similarly, IT tools can predict potential effects on strengths of SR and hnRNP protein recognition sites 23 , 117 . There is no justification for cataloguing intronic and exonic variants, but only assessing splicing effects for the intronic variants or those within natural splice sites 119 , 132 , 175 , 186 , 208 , 210 , 214 , 215 , 248 , 258 , 259 . We recommend that IT-based analysis should evaluate all variants within a gene for potential splicing mutations.…”

Section: Guidelines For Information Theory-based Splicing Mutation Anmentioning

confidence: 99%

Interpretation of mRNA splicing mutations in genetic disease: review of the literature and guidelines for information-theoretical analysis

Caminsky

Mucaki

2014

F1000Res

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The interpretation of genomic variants has become one of the paramount challenges in the post-genome sequencing era. In this review we summarize nearly 20 years of research on the applications of information theory (IT) to interpret coding and non-coding mutations that alter mRNA splicing in rare and common diseases. We compile and summarize the spectrum of published variants analyzed by IT, to provide a broad perspective of the distribution of deleterious natural and cryptic splice site variants detected, as well as those affecting splicing regulatory sequences. Results for natural splice site mutations can be interrogated dynamically with Splicing Mutation Calculator, a companion software program that computes changes in information content for any splice site substitution, linked to corresponding publications containing these mutations. The accuracy of IT-based analysis was assessed in the context of experimentally validated mutations. Because splice site information quantifies binding affinity, IT-based analyses can discern the differences between variants that account for the observed reduced (leaky) versus abolished mRNA splicing. We extend this principle by comparing predicted mutations in natural, cryptic, and regulatory splice sites with observed deleterious phenotypic and benign effects. Our analysis of 1727 variants revealed a number of general principles useful for ensuring portability of these analyses and accurate input and interpretation of mutations. We offer guidelines for optimal use of IT software for interpretation of mRNA splicing mutations.

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Identification of a Novel Splicing Mutation in the ARSA Gene in a Patient with Late-infantile Form of Metachromatic Leukodystrophy

Cited by 12 publications

References 10 publications

Ultra-performance liquid chromatography/tandem mass spectrometry for determination of sulfatides in dried blood spots from patients with metachromatic leukodystrophy

Ultra-performance liquid chromatography/tandem mass spectrometry for determination of sulfatides in dried blood spots from patients with metachromatic leukodystrophy

Untitled

Interpretation of mRNA splicing mutations in genetic disease: review of the literature and guidelines for information-theoretical analysis

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