Becker muscular dystrophy patient with a large intragenic dystrophin deletion: implications for functional minigenes and gene therapy.

Love, Donald R.; Flint, T; Genet, S; Middleton‐Price, Helen; Davies, Kay E.

doi:10.1136/jmg.28.12.860

Cited by 39 publications

(14 citation statements)

References 26 publications

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“…No very obvious connection was found between the location of exons associated with dystrophin synthesis and the exon border codon position. Exons 3,44,45, and 51 have border codon types 3/3, 2/3, 3/2, and 1/3 respectively, compared with codon types of 2/3 and 3/1 for the borders of exons 46 and 52. Boys who were known to have inherited their mutations were just as likely to have low levels of dystrophin as those who were isolated cases.…”

Section: Mutations In Dmd Patients With Low Levels Of Dystrophinmentioning

confidence: 98%

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 2. Correlations within individual patients.

Nicholson¹,

Johnson²,

Bushby³

et al. 1993

Journal of Medical Genetics

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Section: Mutations In Dmd Patients With Low Levels Of Dystrophinmentioning

confidence: 98%

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 2. Correlations within individual patients.

Nicholson¹,

Johnson²,

Bushby³

et al. 1993

Journal of Medical Genetics

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“…In contrast, human muscular dystrophy patients with middle rod domain deletions can present with phenotypes that range from mild to severe (46 -48). Most notably, one frequently cited study described a patient with a middle rod domain deletion who "was able to walk with the aid of a stick at age 61" (46), while a later study (48) from the same group identified additional patients with similar deletions who became wheelchair bound by age 16. It has been suggested that the sarcolemmal membrane of mouse skeletal muscle may experience less mechanical stress per unit area due both to the smaller size of the organism and to the smaller caliber of individual skeletal muscle fibers compared with humans (19,49).…”

Section: Dysr11-17 and Utror11-16 (mentioning

confidence: 99%

Utrophin Lacks the Rod Domain Actin Binding Activity of Dystrophin

Amann¹,

Guo²,

Ervasti³

1999

Journal of Biological Chemistry

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We previously identified a cluster of basic spectrinlike repeats in the dystrophin rod domain that binds F-actin through electrostatic interactions (Amann, K. J., Renley, B. A., and Ervasti, J. M. (1998) J. Biol. Chem. 273, 28419 -28423). Because of the importance of actin binding to the presumed physiological role of dystrophin, we sought to determine whether the autosomal homologue of dystrophin, utrophin, shared this rod domain actin binding activity. We therefore produced recombinant proteins representing the cluster of basic repeats of the dystrophin rod domain (DYSR11-17) or the homologous region of the utrophin rod domain (UTROR11-16). Although UTROR11-16 is 64% similar and 41% identical to DYSR11-17, UTROR11-16 (pI ‫؍‬ 4.86) lacks the basic character of the repeats found in DYSR11-17 (pI ‫؍‬ 7.44). By circular dichroism, gel filtration, and sedimentation velocity analysis, we determined that each purified recombinant protein had adopted a stable, predominantly ␣-helical fold and existed as a highly soluble monomer. DYSR11-17 bound F-actin with an apparent K d of 7.3 ؎ 1.3 M and a molar stoichiometry of 1:5. Significantly, UTROR11-16 failed to bind F-actin at concentrations as high as 100 M. We present these findings as further support for the electrostatic nature of the interaction of the dystrophin rod domain with F-actin and suggest that utrophin interacts with the cytoskeleton in a manner distinct from dystrophin.

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“…Microdeletions in exon 44 led to typical DMD, while gross deletions (approximately 50%) resulted in BMD (Love et al, 1991). Deletions in the central portion and distal rod-like region caused muscle cramps and myalgia, and some other mutations caused asymptomatic high creatine kinase hyperlipidemia (Melis et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Splicing mutation of a gene within the Duchenne muscular dystrophy family

et al. 2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to identify the mutation site and phenotype of the Duchenne muscular dystrophy (DMD) gene in a DMD family. The DMD gene is by far the largest known gene in humans. Up to 34% of the point mutations reported to date affect splice sites of the DMD gene. However, no hotspot mutation has been reported. Capture sequencing of second-generation exons was used to investigate the DMD gene in a proband. Sanger sequencing was performed for mutation scanning in eight family members. Scale-invariant feature transform and PolyPhen were applied to predict the functional impact of protein mutations. A hemizygous splicing mutation IVS44ds +1G-A (c.6438 +1G>A) that induces abnormal splicing variants during late transcription and produces abnormal proteins was located in intron 44. Four missense mutations (p.Arg2937Gln, p.Asp882Gly, p.Lys2366Gln, and p.Arg1745His) that are known multiple-polymorphic sites were found in the coding region of the DMD gene. A heterozygous c.6438 +1G>A mutation was detected on the X chromosome of the proband's mother and maternal grandmother.

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Becker muscular dystrophy patient with a large intragenic dystrophin deletion: implications for functional minigenes and gene therapy.

Cited by 39 publications

References 26 publications

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 2. Correlations within individual patients.

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 2. Correlations within individual patients.

Utrophin Lacks the Rod Domain Actin Binding Activity of Dystrophin

Splicing mutation of a gene within the Duchenne muscular dystrophy family

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