Immunohistochemical alterations of dystrophin in congenital muscular dystrophy

Werneck, Lineu Cesar; Bonilla, Eduardo

doi:10.1590/S0004-282X1995000300008

Abstracts

The dystrophin distribution in the plasma muscle membrane using immunohystochemistry was studied in 22 children with congenital muscular dystrophy. The dystrophin was detected by immunofluorescence in muscle biopsy through a polyclonal antibody. All the cases had patchy interruptions of the fluorescence in the plasma membrane. A large patchy interruption of the sarcolemma was found in 17 cases, small interruption in 12, and a combination of large and small patchy discontinuity in 7. Small gaps around the fiber like a rosary were found in 15 cases. The frequency of these abnormalities ranged cases from: all fibers in 5 cases, frequent in 8, occasional in 5, and rare in 4. Five cases had total absence of immunofluorescence. These results suggest that the dystrophin expression is abnormal in this group of children and that this type of abnormalities can not be differentiated from early Becker muscular dystrophy nor childhood autosomal recessive muscular dystrophy through immunohystochemistry alone.

congenital muscular dystrophy; dystrophin; congenital myopathies

Foi estudada a distribuição da distrofina na membrana plasmática das fibras musculares em 22 crianças com distrofia muscular congênita, através de técnicas de imuno-histoquímica. A distrofina foi identificada nas biópsias musculares processadas a fresco, por técnicas de imunofluorescência utilizando anticorpos policlonais. Todos os casos tinham interrupções da imunofluorescência na membrana plasmática. Em 17 elas eram grandes, em 12 eram pequenas e em 7 eram de ambos os tipos. Fibras com interrupções pequenas e constantes, como um rosário, foram vistas em 15 casos. Essas anormalidades estavam presentes em todas as fibras em 5 casos, eram frequentes em 8, ocasionais em 5 e raras em 4. Cinco casos mostraram fibras sem distrofina. Esses dados sugerem que a expressão da distrofina é anormal nesse grupo de crianças. Essas anormalidades podem também ser encontradas em casos precoces de distrofia muscular de Becker e distrofia autossômica recessiva da infância. Portanto, isoladamente a imuno-histoquímica não permite a diferenciação.

distrofia muscular congênita; distrofina; miopatias congênitas

Lineu Cesar Werneck^I; Eduardo Bonilla^II

^IServiço de Doenças Neuromusculares do Hospital de Clinicas da Universidade Federal do Paraná, Curitiba, Brasil

^IIDepartment of Neurology of the College of Physicians and Surgeons of Columbia University, New York, USA

SUMMARY

The dystrophin distribution in the plasma muscle membrane using immunohystochemistry was studied in 22 children with congenital muscular dystrophy. The dystrophin was detected by immunofluorescence in muscle biopsy through a polyclonal antibody. All the cases had patchy interruptions of the fluorescence in the plasma membrane. A large patchy interruption of the sarcolemma was found in 17 cases, small interruption in 12, and a combination of large and small patchy discontinuity in 7. Small gaps around the fiber like a rosary were found in 15 cases. The frequency of these abnormalities ranged cases from: all fibers in 5 cases, frequent in 8, occasional in 5, and rare in 4. Five cases had total absence of immunofluorescence. These results suggest that the dystrophin expression is abnormal in this group of children and that this type of abnormalities can not be differentiated from early Becker muscular dystrophy nor childhood autosomal recessive muscular dystrophy through immunohystochemistry alone.

Key words:congenital muscular dystrophy, dystrophin, congenital myopathies.

RESUMO

Foi estudada a distribuição da distrofina na membrana plasmática das fibras musculares em 22 crianças com distrofia muscular congênita, através de técnicas de imuno-histoquímica. A distrofina foi identificada nas biópsias musculares processadas a fresco, por técnicas de imunofluorescência utilizando anticorpos policlonais. Todos os casos tinham interrupções da imunofluorescência na membrana plasmática. Em 17 elas eram grandes, em 12 eram pequenas e em 7 eram de ambos os tipos. Fibras com interrupções pequenas e constantes, como um rosário, foram vistas em 15 casos. Essas anormalidades estavam presentes em todas as fibras em 5 casos, eram frequentes em 8, ocasionais em 5 e raras em 4. Cinco casos mostraram fibras sem distrofina. Esses dados sugerem que a expressão da distrofina é anormal nesse grupo de crianças. Essas anormalidades podem também ser encontradas em casos precoces de distrofia muscular de Becker e distrofia autossômica recessiva da infância. Portanto, isoladamente a imuno-histoquímica não permite a diferenciação.

Palavras-chave: distrofia muscular congênita, distrofina, miopatias congênitas.

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Acknowledgments

The authors are grateful to Miss Sumico Nakagawa for the technical assistance and Miss Susana Castilho for the manuscript review.

Aceite: 13-fevereiro-1995.

Dr. Lineu Cesar Wemeck - Hospital de Clínicas, Rua General Carneiro 181, Serviço de Doenças Neuromusculares, 3º andar - 80069-165 Curitiba PR - Brasil.

1. Arahata L, Hoffman EP, Kunkel LM et al. Dystrophin diagnosis: comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses. Proc Nat Acad Sci USA 1989, 86:7154-7158.
2. Arikawa E, Arahata K, Nonaka I, Sugita H. Dystrophin analysis in congenital muscular dystrophy. Neurology 1990, 40 (Suppl):206.
3. Banker BQ. Congenital muscular dystrophy. In: Engel AG, Banker BQ (eds). Myology: basic and clinical. New York: McGraw-Hill, 1986.
4. Beggs AH, Neuman PE, Arahata K et al. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy. Proc Nat Acad Sci USA 1992, 89:623-627.
5. Bonilla E, Samitt CE, Miranda AF et al. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 1988, 54:447-452.
6. Bonilla E, Schmidt B, Samitt CE et al. Normal and dystrophin-deficient muscle fibers in carriers of the gene for Duchenne muscular dystrophy. Am J Pathol 1988, 133:440-445.
7. Bushby KMD, Goodship JA, Nicholson LVB et al. Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy. Neuromusc Disord 1993, 3:57-64.
8. Fukuyana Y, Osawa M, Suzuki H. Congenital progressive muscular dystrophy of the Fukuyma type: clinical, genetic and pathological considerations. Brain & Develop 1981, 3:2-29.
9. Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987, 51:919-928.
10. Hoffman EP, Hudecki MS, Rosemberg PA, Pollina CM, Kunkell LM. Cell and fiber-type distribution of dystrophin. Neuron 1988, 1:411-420.
11. Iannaccone ST, Bove K, Towbin R, Ford LM, Keelber P. Congenital muscular dystrophy. Neurology 1988, 38 (Suppl):187.
12. Matsumura K, Campbell KP. Deficiency of dystrophin-associated proteins: a common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies. Neuromusc Disord 1993, 3:109-118.
13. Matsumura K, Campbell HP. Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophy. Muscle & Nerve 1994, 17:2-15.
14. Matsumura K, Nonaka I, Arahata K, Campbell KP. Partial deficiency of dystrophin-associated protein in a young girl with sporadic myopathy and normal karyotype. Neurology 1993, 43:1267-1268.
15. Matsumura K, Nonaka, I., Campbell KP. Abnormal expression of dystrophin-associated proteins in Fukuyama-type congenital muscular dystrophy. Lancet 1993, 341:521-522.
16. McMenamin JB, Becker LE, Murphy EG. Congenital muscular dystrophy: a clinicopathological report of 24 cases. J Pediatr 1982, 100:692-697.
17. Mendel JR, Iannaccone ST, Burrow KL et al. Dystrophin analysis in congenital muscular dystrophy. Ann Neurol 1990, 28:270.
18. Nonaka I, Sugita H, Takada K, Kumagai K. Muscle histochemistry in congenital muscular dystrophy with central nervous system involvment. Muscle & Nerve 1982, 6:102-106.
19. Ohlencieck K, Matsumura K, Ionasescu VV et al. Duchenne muscular dystrophy: Deficiency of dystrophin-associated proteins in the sarcolemma. Neurology 1993, 43:795-800.
20. Prelle A, Moggio M, Bonilla E et al. Dystrophin deficiency in a congenital myopathy. Neurology 1990, 40(Suppl):207.
21. Serratrice G, Cros D, Pellisier JL, Gastaut JL, Pouget J. Dystrophic musculaire congénitale. Rev Neurol 1980,136:445-472.
22. Werneck LC. The value of muscle biopsy in Neurology: a study of 290 biopsies. Rev Bras Clin Terap 1981, 10(Supl): 2-24.
23. Werneck LC, Bonilla E. Dystrophin in the differentiation between Duchenne and Becker muscular dystrophies: an immunofluorescence study of dystrophin in muscle biopsy related with the clinical stage, serum enzymes and histological findings. Arq Neuropsiquiatr 1990, 48:454-464.

Immunohistochemical alterations of dystrophin in congenital muscular dystrophy

Alterações imuno-hístoquímicas da distrofina na distrofia muscular congênita

Publication Dates

Publication in this collection
09 Dec 2010
Date of issue
Sept 1995

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Arahata L, Hoffman EP, Kunkel LM et al. Dystrophin diagnosis: comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses. Proc Nat Acad Sci USA 1989, 86:7154-7158.

[2] 2. Arikawa E, Arahata K, Nonaka I, Sugita H. Dystrophin analysis in congenital muscular dystrophy. Neurology 1990, 40 (Suppl):206.

[3] 3. Banker BQ. Congenital muscular dystrophy. In: Engel AG, Banker BQ (eds). Myology: basic and clinical. New York: McGraw-Hill, 1986.

[4] 4. Beggs AH, Neuman PE, Arahata K et al. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy. Proc Nat Acad Sci USA 1992, 89:623-627.

[5] 5. Bonilla E, Samitt CE, Miranda AF et al. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell 1988, 54:447-452.

[6] 6. Bonilla E, Schmidt B, Samitt CE et al. Normal and dystrophin-deficient muscle fibers in carriers of the gene for Duchenne muscular dystrophy. Am J Pathol 1988, 133:440-445.

[7] 7. Bushby KMD, Goodship JA, Nicholson LVB et al. Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy. Neuromusc Disord 1993, 3:57-64.

[8] 8. Fukuyana Y, Osawa M, Suzuki H. Congenital progressive muscular dystrophy of the Fukuyma type: clinical, genetic and pathological considerations. Brain & Develop 1981, 3:2-29.

[9] 9. Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987, 51:919-928.

[10] 10. Hoffman EP, Hudecki MS, Rosemberg PA, Pollina CM, Kunkell LM. Cell and fiber-type distribution of dystrophin. Neuron 1988, 1:411-420.

[11] 11. Iannaccone ST, Bove K, Towbin R, Ford LM, Keelber P. Congenital muscular dystrophy. Neurology 1988, 38 (Suppl):187.

[12] 12. Matsumura K, Campbell KP. Deficiency of dystrophin-associated proteins: a common mechanism leading to muscle cell necrosis in severe childhood muscular dystrophies. Neuromusc Disord 1993, 3:109-118.

[13] 13. Matsumura K, Campbell HP. Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophy. Muscle & Nerve 1994, 17:2-15.

[14] 14. Matsumura K, Nonaka I, Arahata K, Campbell KP. Partial deficiency of dystrophin-associated protein in a young girl with sporadic myopathy and normal karyotype. Neurology 1993, 43:1267-1268.

[15] 15. Matsumura K, Nonaka, I., Campbell KP. Abnormal expression of dystrophin-associated proteins in Fukuyama-type congenital muscular dystrophy. Lancet 1993, 341:521-522.

[16] 16. McMenamin JB, Becker LE, Murphy EG. Congenital muscular dystrophy: a clinicopathological report of 24 cases. J Pediatr 1982, 100:692-697.

[17] 17. Mendel JR, Iannaccone ST, Burrow KL et al. Dystrophin analysis in congenital muscular dystrophy. Ann Neurol 1990, 28:270.

[18] 18. Nonaka I, Sugita H, Takada K, Kumagai K. Muscle histochemistry in congenital muscular dystrophy with central nervous system involvment. Muscle & Nerve 1982, 6:102-106.

[19] 19. Ohlencieck K, Matsumura K, Ionasescu VV et al. Duchenne muscular dystrophy: Deficiency of dystrophin-associated proteins in the sarcolemma. Neurology 1993, 43:795-800.

[20] 20. Prelle A, Moggio M, Bonilla E et al. Dystrophin deficiency in a congenital myopathy. Neurology 1990, 40(Suppl):207.

[21] 21. Serratrice G, Cros D, Pellisier JL, Gastaut JL, Pouget J. Dystrophic musculaire congénitale. Rev Neurol 1980,136:445-472.

[22] 22. Werneck LC. The value of muscle biopsy in Neurology: a study of 290 biopsies. Rev Bras Clin Terap 1981, 10(Supl): 2-24.

[23] 23. Werneck LC, Bonilla E. Dystrophin in the differentiation between Duchenne and Becker muscular dystrophies: an immunofluorescence study of dystrophin in muscle biopsy related with the clinical stage, serum enzymes and histological findings. Arq Neuropsiquiatr 1990, 48:454-464.