Carrier detection of duchenne and becker muscular dystrophy using muscle dystrophin immunohistochemistry

Oliveira, Acary S. Bulle; Gabbai, Alberto A.; Schmidt, Beny; Hitomi Kiyomoto, Beatriz; Lima, G. Camargo; Minetti, Carlo; Bonilla, Eduardo

doi:10.1590/S0004-282X1992000400010

Abstracts

To ascertain whether dystrophin immunohistochemistry could improve DMD/ BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, KMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measuremens, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.

muscular dystrophy (Duchenne and Becker); carrier detection; dystrophin

Para determinar se imuno-histoquímica com distrofina poderia melhorar a detecção de portadoras de distrofia muscular de Duchenne (DMD) e de Becker (DMB), analisamos 14 biópsias musculares de 13 portadoras prováveis ou possíveis de DMD e de uma portadora provável de DMB. Todas as mulheres foram também avaliadas usando métodos convencionais, incluindo análise genética, avaliação clínica e neurológica, níveis séricos de CK, EMG e biópsia muscular com estudo histoquímico. Em 6 casos havia um mosaico de fibras musculares distrofina-positivas e distrofina-negativas, que permitia caracterizar um estado de portadora. Comparando imuno-histoquímica com distrofina e métodos tradicionais, notou-se que este método é menos sensível que medidas de CK, mas é mais sensível que EMG e biópsia muscular. O uso deste método associado a CK, EMG e biópsia muscular aumentou ta possibilidade de detecção de portadoras. Este método é também útil para distinguir portadoras manifestantes de DMD de pacientes com outras doenças neuromusculares como a distrofia cintura-membros e amiotrofia espinhal progressiva,

distrofia muscular (Duchenne e Becker); detecção de portadoras; distrofina

Acary S. Bulle Oliveira^I; Alberto A. Gabbai^I; Beny Schmidt^II; Beatriz Hitomi Kiyomoto^I; J. G. Camargo Lima^I; Carlo Minetti^III; Eduardo Bonilla^III

^IDepartement of Neurology, Neurosurgery and Experimental Neurology of Escola Pau-lista de Medicina (EPM), São Paulo

^IIAdjunct Professor, Department of Pathology, EPM

^IIIDepartment of Neurology, College of Physicians and Surgeons of Columbia University, New York

SUMMARY

To ascertain whether dystrophin immunohistochemistry could improve DMD/ BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, KMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measuremens, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.

Key words: muscular dystrophy (Duchenne and Becker), carrier detection, dystrophin.

RESUMO

Para determinar se imuno-histoquímica com distrofina poderia melhorar a detecção de portadoras de distrofia muscular de Duchenne (DMD) e de Becker (DMB), analisamos 14 biópsias musculares de 13 portadoras prováveis ou possíveis de DMD e de uma portadora provável de DMB. Todas as mulheres foram também avaliadas usando métodos convencionais, incluindo análise genética, avaliação clínica e neurológica, níveis séricos de CK, EMG e biópsia muscular com estudo histoquímico. Em 6 casos havia um mosaico de fibras musculares distrofina-positivas e distrofina-negativas, que permitia caracterizar um estado de portadora. Comparando imuno-histoquímica com distrofina e métodos tradicionais, notou-se que este método é menos sensível que medidas de CK, mas é mais sensível que EMG e biópsia muscular. O uso deste método associado a CK, EMG e biópsia muscular aumentou ta possibilidade de detecção de portadoras. Este método é também útil para distinguir portadoras manifestantes de DMD de pacientes com outras doenças neuromusculares como a distrofia cintura-membros e amiotrofia espinhal progressiva,

Palavras-chave: distrofia muscular (Duchenne e Becker), detecção de portadoras, distrofina.

Texto completo disponível apenas em PDF.

Full text available only in PDF format.

Supported partially by the Brazilian Research Council (CNPq).

Dr. Acary Souza Bulle Oliveira Disciplina de Neurologia, Escola Paulista de Medicina -Rua Botucatu 762 - 04028 São Paulo SP - Brasil.

1. Bonilla E, Schmidt B, Samitt CE, Miranda AF, Hays AP, Oliveira ASB, Chang HW, Servidei S, Ricci E, Younger DS, DiMauro S. Normal and dystrophin deficient muscle fibers in carriers of the gene for Duchenne muscular dystrophy. Am J Pathol 1988, 133:440-445.
2. Comi G, Comola M, Galardi G. Piattoni F, Erembourg L, Canal N. Individuazione delle portatrici della distrofia muscolare di Duchenne: problemi e prospective. Minerva Pediat 1986, 38:625-632.
3. Dubowitz V, Brooke M. Muscle biopsy: a modern approach. London: W.B. Saunders, 1973.
4. Emery ASH. The muscular dystrophies. In Emery AEH, Rimoin D (eds) : Principles and Practice of Medical Genetics. Edinburgh: Churchill Livingstone, 1983, p 332-411.
5. England SB, Nicholson LVB, Johnson MA, et al. Very mild muscular dystrophy associated with deletion of 46% of dystrophin. Nature 1990, 343:180-182.
6. Gutmann DH, Fischbeck KH. Molecular biology of Duchenne and Becker's muscular dystrophy : clinical applications. Ann Neurol 1989, 26:189-190.
7. Kendal HO, Kendal FP, Wadsworth GE. Muscle testing and function. Ed 2. Baltimore: Williams and Wilkins, 1971.
8. Lyon MF. Sex chromatin and gene action in the mammalian X-chromosome. Am J Human Genet 1962, 14:135-148.
9. Milhorat AT, Goldstone L. The carrier state in muscular dystrophy of the Duchenne type: identification by serum creatine-kinase level. JAMA 1965, 194:130-134.
10. Yates JRW, Emery AEH. A population study of adult onset limb-girdle muscular dystrophy. J Med Genet 1985, 22:250-257.
11. Werneck LC, Bonilla E. Distrofina na diferenciação das distrofias de Duchenne e Becker: estudo imuno-histoquímico comparado com o estado clínico, enzimas séricas e biópsia muscular. Arq Neuro-Psiquiatr 1990, 48:454-464.
12. Zellweger H, Ionasescu V, Simpsom J. Sporadic Duchenne muscular dystrophy in females: genetic counseling of women with pelvifemoral muscular dystrophy. Helvet Paed Acta 1980, 35:343-348.

Carrier detection of duchenne and becker muscular dystrophy using muscle dystrophin immunohistochemistry

Detecção de portadoras de distrofia muscular de Duchenne e de Becker utilizando imuno-hitoquímica com distrofina

Publication Dates

Publication in this collection
22 Feb 2011
Date of issue
Dec 1992

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

[1] 1. Bonilla E, Schmidt B, Samitt CE, Miranda AF, Hays AP, Oliveira ASB, Chang HW, Servidei S, Ricci E, Younger DS, DiMauro S. Normal and dystrophin deficient muscle fibers in carriers of the gene for Duchenne muscular dystrophy. Am J Pathol 1988, 133:440-445.

[2] 2. Comi G, Comola M, Galardi G. Piattoni F, Erembourg L, Canal N. Individuazione delle portatrici della distrofia muscolare di Duchenne: problemi e prospective. Minerva Pediat 1986, 38:625-632.

[3] 3. Dubowitz V, Brooke M. Muscle biopsy: a modern approach. London: W.B. Saunders, 1973.

[4] 4. Emery ASH. The muscular dystrophies. In Emery AEH, Rimoin D (eds) : Principles and Practice of Medical Genetics. Edinburgh: Churchill Livingstone, 1983, p 332-411.

[5] 5. England SB, Nicholson LVB, Johnson MA, et al. Very mild muscular dystrophy associated with deletion of 46% of dystrophin. Nature 1990, 343:180-182.

[6] 6. Gutmann DH, Fischbeck KH. Molecular biology of Duchenne and Becker's muscular dystrophy : clinical applications. Ann Neurol 1989, 26:189-190.

[7] 7. Kendal HO, Kendal FP, Wadsworth GE. Muscle testing and function. Ed 2. Baltimore: Williams and Wilkins, 1971.

[8] 8. Lyon MF. Sex chromatin and gene action in the mammalian X-chromosome. Am J Human Genet 1962, 14:135-148.

[9] 9. Milhorat AT, Goldstone L. The carrier state in muscular dystrophy of the Duchenne type: identification by serum creatine-kinase level. JAMA 1965, 194:130-134.

[10] 10. Yates JRW, Emery AEH. A population study of adult onset limb-girdle muscular dystrophy. J Med Genet 1985, 22:250-257.

[11] 11. Werneck LC, Bonilla E. Distrofina na diferenciação das distrofias de Duchenne e Becker: estudo imuno-histoquímico comparado com o estado clínico, enzimas séricas e biópsia muscular. Arq Neuro-Psiquiatr 1990, 48:454-464.

[12] 12. Zellweger H, Ionasescu V, Simpsom J. Sporadic Duchenne muscular dystrophy in females: genetic counseling of women with pelvifemoral muscular dystrophy. Helvet Paed Acta 1980, 35:343-348.