Partial gene duplication in Duchenne and Becker muscular dystrophies.

Hu, Xiheng; Burghes, Arthur; Ray, Peter N.; Thompson, Margaret; Murphy, Ellen; Worton, R G

doi:10.1136/jmg.25.6.369

Cited by 69 publications

(32 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The multiplex reactions were not performed because the isolated one is more credible and compatible with the conditions of our laboratory. The exons studied were numbers 3,4,6,8,12,13,17,19,42,43,44,45,47,48,50, 51, 52 ,53, 60 and Pm. The PCR products were analyzed on a 7% polyacrylamide gel and the bands visualized by silver staining 19 .…”

Section: Methodsmentioning

confidence: 99%

“…The milder BMD, on the oth-er hand, is caused by internal mutations that do not disrupt the reading frame, so partially functional protein can still be produced 11,12 . In the past, deletions and duplications of the dystrophin gene were detected by Southern-blot analysis using cDNA probes 9,10,13 . Nowadays, deletions are detected in many DMD/BMD patients by a series of PCR assays 14 .…”

Section: Distrofia Muscular De Duchenne E Becker: Abordagem Molecularmentioning

confidence: 99%

See 1 more Smart Citation

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Freund

Scola

Arndt

et al. 2007

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

-Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains). The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.KEY WORDS: Duchenne muscular dystrophy, Becker muscular dystrophy, immunohistochemistry, PCR, deletions, exons. Distrofia muscular de Duchenne e Becker: abordagem molecular e imuno-histoquímicaRESUMO -As distrofias musculares de Duchenne (DMD) e de Becker (DMB) são doenças causadas por mutação no gene da distrofina. Foram estudados 106 casos com a suspeita diagnóstica de DMD/BMD com a analise de 20 exons do gene da distrofina no sangue e biópsia muscular com imuno-histoquímica para distrofina em alguns casos. Em 71,7% dos casos foi encontrada deleção em pelo menos um dos exons, sendo que 68% das deleções localizam-se na região 3´ hot spot. Foram encontradas deleções em 81,5% dos DMD e em todos os BMD, sendo que os sem deleção tinham deficiência de distrofina, incluindo a mulher com DMD. As portadoras sintomáticas não tinham deleções mas anormalidades na distribuição da distrofina no sarcolema. Os outros casos sem deleção, com auxilio da biópsia muscular tiveram outros diagnósticos (atrofia muscular espinhal, miopatia congênita, deficiência de sarcoglicanos, distrofia de cinturasmembros sem classificação). A análise imuno-histoquímica para distrofina na biópsia muscular continua sendo o método mais específico para diagnóstico de DMD/DMB e deve ser utilizado quando não são encontradas deleções do gene da distrophina no sangue.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Distrofia Muscular De Duchenne E Becker: Abordagem Molecularmentioning

confidence: 99%

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Freund

Scola

Arndt

et al. 2007

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

show abstract

“…7,22,23 Despite using different primer combinations, it was impossible to characterize the duplication breakpoints for this patient and his relative. In case 2, the recombination between the normal X chromosome and intron 22 inversion of the sister X chromosome produced a more complex rearrangement without maintaining a complete copy of the F8 gene (Figure 3).…”

Section: Intron 22 Homologous Regions N Lannoy Et Almentioning

confidence: 99%

Intron 22 homologous regions are implicated in exons 1–22 duplications of the F8 gene

et al. 2013

View full text Add to dashboard Cite

The intron 22 inversion found in up to 50% of severe hemophilia A patients results from a recombination between three intron 22 homologous copies (int22h). This study evaluated the implication of these copies in the formation of extended duplications comprising exons 1-22 of the factor 8 (F8) gene and their association with hemophilia and mental retardation. Two hemophilic patients with moderate and severe phenotypes and a third nonhemophilic patient with developmental delay were studied. All exhibited a duplication of F8 gene exons 1-22 identified by multiplex ligation-dependent probe amplification along with abnormal patterns on Southern blotting and unexpected long-range PCR amplification. Breakpoint analysis using array comparative genomic hybridization was performed to delimit the extent of these rearrangements. These duplications were bounded on one side by the F8 intragenic int22h-1 repeat and on the other side by extragenic int22h-2 or int22h-3 copies. However, the simultaneous identification of a second duplication containing F8 gene exons 2-14 for the moderate patient and the classical intron 22 inversion for the severe patient are considered in this study as the genetic causal defects of hemophilia. This study shows that the well-known int22h copies are involved in extended duplications comprising F8 gene exons 1-22. These specific duplications are probably not responsible for hemophilia and intellectual disability, but should be carefully considered in genetic counseling, while continuing to investigate the causal mutation of hemophilia.

show abstract

“…2,3 Exons 3,4,6,8,12,13,17,19,43, 44, 47, 50, 51, 52 and 60 were amplified either as triplex (A-C) or duplex sets (D-F) for each patient. Exons to be analysed together on a single SSCA gel were carefully selected according to their size and the location of their singlestranded patterns on the selected gel system.…”

Section: Pcr Conditionsmentioning

confidence: 99%

“…2,3 A small proportion of mutations (6%) are duplications. 4 Small mutations, including point mutations or microdeletions/insertions, are the cause of the disease in the remaining DMD/BMD cases, therefore it is very important to find the underlying defect in these group of patients. 203 different mutations have been identified and reported to the Muscular Dystrophy (Point) Mutation Database so far.…”

Section: Introductionmentioning

confidence: 99%

Identification of point mutations in Turkish DMD/BMD families using multiplex-single stranded conformation analysis (SSCA)

Eraslan¹,

Kayserili

Apak

et al. 1999

Eur J Hum Genet

View full text Add to dashboard Cite

Small mutations are the cause of the disease in one third of cases of Duchenne and Becker muscular dystrophy (DMD/BMD). The identification of point mutations in the dystrophin gene is considered to be very important, because it may provide new insights into the function of dystrophin and direct information for genetic counselling. In this study, we have screened 18 deletion-prone exons (25.5% of the coding region) of the dystrophin gene by using a modified non-isotopic multiplex single-stranded conformation analysis (SSCA). Mutations responsible for the disease phenotype could be identified in five out of 56 unrelated DMD/ BMD patients without detectable deletions. Two of these mutations, 980-981delCC and 719G > C, are novel mutations which have not been described previously. Four of the five mutations, including 980-981delCC detected in this study are found to be nonsense or frameshift mutations leading to the synthesis of a truncated dystrophin protein. The missense mutation, 719G > C, causing the substitution of highly conserved alanine residue at 171 with proline in the actin binding domain of the dystrophin, is associated with a BMD phenotype. This study also revealed the presence of six polymorphisms in Turkish DMD/BMD patients.

show abstract

Partial gene duplication in Duchenne and Becker muscular dystrophies.

Cited by 69 publications

References 25 publications

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Intron 22 homologous regions are implicated in exons 1–22 duplications of the F8 gene

Identification of point mutations in Turkish DMD/BMD families using multiplex-single stranded conformation analysis (SSCA)

Contact Info

Product

Resources

About