Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 3. Differential diagnosis and prognosis.

Nicholson, L. V. B.; Johnson, Margaret; Bushby, Kate; Gardner-Medwin, D.; Curtis, Ann; Ginjaar, I. B.; Dunnen, Johan T. den; Welch, John L.; Butler, Thomas J.; Bakker, Egbert

doi:10.1136/jmg.30.9.745

Cited by 36 publications

(18 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis shows that in frame deletions in this region can result in great phenotypic variability, and not always in BMD, confirming what is reported in this study. In particular, deletions of exons 2-7, 3, 3-9, 5-13, 6-13, and [10][11][12][13] have been frequently associated with disease courses more severe than expected (table 2).…”

Section: Discussionmentioning

confidence: 99%

Deletions in the 5' region of dystrophin and resulting phenotypes.

Muntoni

Gobbi

Sewry

et al. 1994

Journal of Medical Genetics

View full text Add to dashboard Cite

Deletions in the dystrophin gene give rise to both Duchenne and Becker muscular dystrophies. Good correlation is generally found between the severity of the phenotype and the effect of the deletion on the reading frame: deletions that disrupt the reading frame result in a severe phenotype, while in frame deletions are associated with a milder disease course. Rare exceptions to this rule, mainly owing to frameshift mutations in the 5' region of the gene (in particular deletions involving exons 3 to 7) which are associated with a milder than expected phenotype, have been reported previously. In order to characterise better the relationship between genotype and phenotype as a result ofmutations arising in the 5' region of the gene, we have studied a large cohort of patients with smali in frame and out of frame deletions in the first 13 exons of the dystrophin gene. Fifty-five patients with a deletion in this area were identified; approximately one third of them had a phenotype different from that theoretically expected. Patients were divided into two groups: (1) patients with a severe clinical phenotype despite the presence of a small, in frame deletion and (2) patients with a mild phenotype and an out of frame deletion. Noticeable examples observed in the first group were Duchenne boys with a deletion ofexon 5, ofexon 3, and ofexons 3-13. In the second group we observed several patients with an intermediate or Becker phenotype and out of frame deletions involving not only the usual exons 3-7 but also 5-7 and 3-6. These data indicate that a high proportion of patients with a deletion in the 5' end of the gene have a phenotype that is not predictable on the basis of the effect of the deletion on the reading frame. The N-terminus of dystrophin has at least one actin binding domain that might be affected by the small, in frame deletions in this area. The effect of the in frame deletions of exon 3, 5, and 3-13 on this domain might account for the severe phenotype observed in these patients. Other mechanisms, such as unexpected effect of the deletion on splicing behaviour, might, however, also be implicated in determinining the phenotype outcome. (JMed Genet 1994;31:843-847) Duchenne and Becker muscular dystrophies (DMD and BMD) both arise from mutations in the dystrophin gene.'2 In the majority of patients affected by DMD and BMD, a deletion affecting one or more exons of the dystrophin gene is found after either Southern blotting or polymerase chain reaction (PCR) study of genomic DNA.`-5 In general the effect of the deletion on the reading frame was found to be in good agreement with the severity of the observed phenotype: deletions causing a frameshift were generally found to be associated with a severe DMD phenotype (irrespective of the size of the deletion), while deletions not affecting the reading frame were found to be associated with the milder BMD phenotype.6Exceptions to this general rule have also been identified for both types of mutations. In particular, BMD or intermediate DMD/BMD phenotypes h...

show abstract

Section: Discussionmentioning

confidence: 99%

Deletions in the 5' region of dystrophin and resulting phenotypes.

Muntoni

Gobbi

Sewry

et al. 1994

Journal of Medical Genetics

View full text Add to dashboard Cite

show abstract

“…Deletions were found in 63%, a percentage in accordance with other unselected series of DMD patients. 27 Dystrophin can be shown in the retina by immunohistochemical methods. Transcription of the dystrophin gene involves at least five distinct promoters, each of them driving cell specific dystrophins.28 Different dystrophins are present in the brain, muscle, Purkinje cells, Schwann cells, and glial cells,28 and are transcribed by alternative splicing.…”

Section: ;mentioning

confidence: 99%

Duchenne muscular dystrophy: negative electroretinograms and normal dark adaptation. Reappraisal of assignment of X linked incomplete congenital stationary night blindness.

Jensen

Warburg

Sjö

et al. 1995

Journal of Medical Genetics

View full text Add to dashboard Cite

Xp21. Sigesmund et a120 described 26 patients with DMD/BMD. Five patients, ofwhom three were brothers, had electroretinographic b/a amplitude ratios <10. Their deletions were exons 14-41, 48-49, and 45. Ten patients had no deletions and four of them had a b/a ratio < 1 0. The rest had normal b/a amplitude ratios. No dark adaptation thresholds were routinely examined in the studies mentioned.We have observed eight boys with DMD/ BMD resulting from deletions downstream from exon 44. The ERGs had a b/a amplitude ratio <1 0, dark adaptation thresholds were normal, and there were no visual functional defects. We conclude that a negative ERG associated with deletion of the dystrophin gene is insufficient evidence for mapping CSNB and AIED to Xp2l.

show abstract

“…In Becker muscular dystrophy the amount of dystrophin is normal or near normal, but the protein is often smaller than normal and a segment corresponding to the deletion in the gene is missing.5 New techniques for investigating the dystrophin gene and gene product have shown that dystrophinopathy may be expressed clinically in many different waysfor example, as muscle cramps as the only symptom or high serum creatine kinase (s-CK) as the only evidence of muscle disease. [6][7][8][9] Female carriers of the mutation usually are symptom free, but some have symptoms. In some cases this may be due to a non-random inactivation of the X chromosomes, leading to a predominant expression of the X chromosome that has a mutation in the dystrophin gene.…”

mentioning

confidence: 99%

Dilated cardiomyopathy and the dystrophin gene: an illustrated review.

Oldfors

Eriksson

Kyllerman

et al. 1994

Heart

View full text Add to dashboard Cite

Cardiomyopathy is often found in patients with Duchenne and Becker muscular dystrophy, which are X linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects present in many different ways and cases of mild Becker muscular dystrophy have been described in which cardiomyopathy was severe. Female carriers of Duchenne muscular dystrophy can develop symptomatic skeletal myopathy alone or combined with dilated cardiomyopathy. They can also develop dilated cardiomyopathy alone. X linked dilated cardiomyopathy has been found in association with dystrophin defects. The relation between the molecular defects and the cardiac phenotypes has not yet been established. New mutations in the dystrophin gene are common and such mutations cause one third of the cases with Duchenne and Becker muscular dystrophy. This means that sporadic cases of cardiomyopathy caused by dystrophin defects are likely. This paper reports such a case in a boy of 14 who died of dilated cardiomyopathy. Before the cardiac investigation, which was performed one month before he died, he had not complained of muscular weakness. He had minor signs of limb girdle myopathy and slightly increased concentrations of serum creatine kinase. He was found to have an unusual deletion in the dystrophin gene.

show abstract

Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 3. Differential diagnosis and prognosis.

Abstract: This report is the third part of a trilogy from a multidisciplinary study which was undertaken to investigate

Cited by 36 publications

References 41 publications

Deletions in the 5' region of dystrophin and resulting phenotypes.

Deletions in the 5' region of dystrophin and resulting phenotypes.

Duchenne muscular dystrophy: negative electroretinograms and normal dark adaptation. Reappraisal of assignment of X linked incomplete congenital stationary night blindness.

Dilated cardiomyopathy and the dystrophin gene: an illustrated review.

Contact Info

Product

Resources

About