Pattern of deletions of the dystrophin gene in Mexican Duchenne/Becker muscular dystrophy patients: The use of new designed primers for the analysis of the major deletion “hot spot” region

Coral‐Vázquez, Ramón; Arenas, Diego; Cisneros, Bulmaro; Peñaloza, Laura; Salamanca, Fabio; Kofman, Susana; Mercado, Rosalio; Montañez, Cecilia

doi:10.1002/(sici)1096-8628(19970613)70:3<240::aid-ajmg5>3.0.co;2-#

Cited by 10 publications

(6 citation statements)

References 30 publications

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“…Deletions in the patients studied were most frequent in exons 45 and 43. All these findings are similar to those described by other authors [25][26][27] . The deletion frequency of 71.7% is different to that found previously in another study 27 , in which DNA was extracted from impaired muscular tissue.…”

Section: Discussionsupporting

confidence: 93%

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Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Freund

Scola

Arndt

et al. 2007

Arq. Neuro-Psiquiatr.

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-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.

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Section: Discussionsupporting

confidence: 93%

“…In the present study, however, we used DNA extracted from leukocytes. We found similar frequencies to those described in the current literature 14,17,18,25 . It is possible that by using leukocytes we were not able to find deletions caused by somatic mosaicism or germ-line cells 27 .…”

Section: Discussionsupporting

confidence: 90%

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Freund

Scola

Arndt

et al. 2007

Arq. Neuro-Psiquiatr.

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“…1). The hot spot placed in the core region (exons 44±53) presented fewer deletions than those described by current literature [Baumbach et al, 1989;den Dunnen et al, 1989;Gillard et al, 1989;Lindlof et al, 1989;Coral-Va Â zquez et al, 1997].…”

Section: Discussionmentioning

confidence: 71%

“…Clinical/molecular correlation based on the reading frame alterations are present in 92% [Koenig et al, 1989]. Despite the large dimension of this gene, partial deletions and duplications cluster in two hot-spot regions: 1) the 5 H terminal gene portion that includes exons 2±20 accounting for nearly 30%; 2) central rod domain, including exons 44±53 where almost 70% of deletions are detected [Baumbach et al, 1989;den Dunnen et al, 1989;Gillard et al, 1989;Lindlof et al, 1989;Coral-Va Â zquez et al, 1997]. These deletions can be found either by Southern blotting, using speci®c cDNA [Gillard et al, 1989;Koenig et al, 1989;Passos-Bueno et al, 1990;Falca Ä o-Conceic Ëa Ä o et al, 1992] or by PCR.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of PCR-deletion detection and immunohistochemistry in Brazilian Duchenne and Becker muscular dystrophy patients

et al. 2001

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We studied 48 patients with dystrophinopathies (29 Duchenne muscular dystrophy (DMD), 13 Becker muscular dystrophy (BMD), four possible carriers, one female with DMD, and one intermediate form, using polymerase chain reaction (PCR) analysis of muscle tissue for 20 exons and compared them with immunohistochemistry studies for dystrophin. Of these, 42 (87.5%) showed at least one intragenic deletion. Most of them (47.45%) involved exons 2 to 20. All BMD patients presented deletions on the dystrophin gene. The 29 patients with DMD showed abnormal dystrophin in immunohistochemistry studies, some with total absence (17/29), others with residual (3/29), and the remaining with scattered positive fiber (9/29). The majority of the 13 patients with BMD had abnormal immunohistochemistry studies with diffuse reduction in the majority of muscle fibers (10/13), a few with patch discontinuation in the sarcolemma (2/13), and one normal (1/13). The immunohistochemistry exam for dystrophin is still the gold-standard method for DMD/BMD diagnosis. An ethnic difference, the analysis of several exons, the sample size, and the use of muscle tissue could explain this high frequency of deletions in the dystrophin gene found in our cases.

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“…The muscular weakness is progressive, causing loss of ambulation by early adolescence (between 9 and 12 years of age) [ 1 ]. DMD is caused by mutations in the DMD gene that code for dystrophin, a sarcolemmal cytoskeletal protein [ 2 – 4 ]. DMD gene mutations that result in complete loss of dystrophin interrupt their translation, giving rise to DMD.…”

Section: Introductionmentioning

confidence: 99%

Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

Rodríguez‐Cruz

Sánchez

Escobar

et al. 2015

International Journal of Endocrinology

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Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16–74.69) and 50 (OR = 8.73; 95% CI = 1.17–65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.

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Pattern of deletions of the dystrophin gene in Mexican Duchenne/Becker muscular dystrophy patients: The use of new designed primers for the analysis of the major deletion “hot spot” region

Cited by 10 publications

References 30 publications

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach

Comparative analysis of PCR-deletion detection and immunohistochemistry in Brazilian Duchenne and Becker muscular dystrophy patients

Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

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