Are CpG sites mutation hot spots in the dystrophin gene?

Akalin, Nur; Ziętkiewicz, Ewa; Makałowski, Wojciech; Labuda, Damian

doi:10.1093/hmg/3.8.1425

Cited by 16 publications

(11 citation statements)

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“…Three of the four nonsense mutations occur in CGA codons; as seen in other genes, methylable CpG-dinucleotides constitute preferential sites for nonsense mutations, because of an increased mutation rate for C-to-T transitions through oxidative deamination of 5-methylcytosine. The two recurrent mutations (R3190X and R3391X) in our sample and 8 of 11 (73%) recurrent nonsense substitutions reported in a recent database (den Dunnen et al 1996, web information) arose in one of the 28 potential stop codons attributable to transitions at CpG sites listed in the dystrophin coding sequence (Akalin et al 1994). We have also observed that 13 of 50 (26%) nonsense mutations in the database occur at these sites, whereas they represent only 2.2% (28/1738) of the overall potential sites for nonsense mutations.…”

Section: Point Mutation Analysismentioning

confidence: 55%

Mutation analysis of the dystrophin gene in Southern French DMD or BMD families: from Southern blot to protein truncation test

Tuffery¹,

Chambert²,

Bareil³

et al. 1998

Human Genetics

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Data from 6 years of experience in molecular diagnosis of Duchenne (DMD) and Becker (BMD) muscular dystrophy in Southern France are reported. DMD and BMD patients have been extensively analyzed for deletions and for point mutations in the dystrophin gene. By scanning the whole coding sequence as reverse-transcribed from lymphocytes or muscular RNA by the protein truncation test, we have reached a minimum of an 86% detection rate for point mutations responsible for DMD; these mutations consist of nonsense, frameshifting, and splicing mutations. Four of 12 small alterations identified in our sample are novel and described in this study. We also present an improved protocol for the automated detection of fluorescently labeled duplex polymerase chain reactions of six known intragenic microsatellites (Dys II, TG 15, STRs 44, 45, 49, and 50). Accurate sizing of the alleles at each locus was performed, and we elucidated the sequence of several repeat units. Allele frequencies at each of the six microsatellite loci and at one restriction fragment length polymorphism site (intron 16/TaqI) were defined in a sample of normal, DMD, and BMD X chromosomes from Southern France. The determination of the grandparental origin of either deletions or point mutations revealed differences depending on the type of the mutation, with most of the deletions occurring in oogenesis and most of the point mutations occurring in spermatogenesis.

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Section: Point Mutation Analysismentioning

confidence: 55%

Mutation analysis of the dystrophin gene in Southern French DMD or BMD families: from Southern blot to protein truncation test

Tuffery¹,

Chambert²,

Bareil³

et al. 1998

Human Genetics

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“…Además, en la distrofina existen 29 codones CGA (arginina), y en este estudio se ha identificado la transición de la citosina a timina en 11 de ellos. Varios estudios publicados con anterioridad ya observaron esta tendencia a la transición a timina de las citosinas metiladas de los dinucleótidos CpG por desaminación espontánea, por lo que estos dinucleóti-dos CpG son puntos calientes de mutaciones en el gen de la distrofina 11,32,33,36,37 .…”

Section: Discussionunclassified

Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos

et al. 2017

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“…These C-to-T transitions all lie in a CGA codon where a C-to-T transition changes an Arg codon to a stop codon (TGA). They are distributed over 23 out of the 28 CpG targets for nonsense mutations in the dystrophin coding region [Akalin et al, 1994]. No mutation at the CpG dinucleotide located in exons 9, 21, 32, 61, and 76 were found (Fig.…”

Section: Nonsense Mutationsmentioning

confidence: 97%

Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase

et al. 2009

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UMD-DMD France is a knowledgebase developed through a multicenter academic effort to provide an up-to-date resource of curated information covering all identified mutations in patients with a dystrophinopathy. The current release includes 2,411 entries consisting in 2,084 independent mutational events identified in 2,046 male patients and 38 expressing females, which corresponds to an estimated number of 39 people per million with a genetic diagnosis of dystrophinopathy in France. Mutations consist in 1,404 large deletions, 215 large duplications, and 465 small rearrangements, of which 39.8% are nonsense mutations. The reading frame rule holds true for 96% of the DMD patients and 93% of the BMD patients. Quality control relies on the curation by four experts for the DMD gene and related diseases. Data on dystrophin and RNA analysis, phenotypic groups, and transmission are also available. About 24% of the mutations are de novo events. This national centralized resource will contribute to a greater understanding of prevalence of dystrophinopathies in France, and in particular, of the true frequency of BMD, which was found to be almost half (43%) that of DMD. UMD-DMD is a searchable anonymous database that includes numerous newly developed tools, which can benefit to all the scientific community interested in dystrophinopathies. Dedicated functions for genotypebased therapies allowed the prediction of a new multiexon skipping (del 45-53) potentially applicable to 53% of the deleted DMD patients. Finally, such a national database will prove to be useful to implement the international global DMD patients' registries under development. Hum Mutat 30,[934][935][936][937][938][939][940][941][942][943][944][945]

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Are CpG sites mutation hot spots in the dystrophin gene?

Cited by 16 publications

References 0 publications

Mutation analysis of the dystrophin gene in Southern French DMD or BMD families: from Southern blot to protein truncation test

Mutation analysis of the dystrophin gene in Southern French DMD or BMD families: from Southern blot to protein truncation test

Espectro mutacional de la distrofia muscular de Duchenne en España: estudio de 284 casos

Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase

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