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 »  Case report
 »  Materials and me...
 »  Results
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 »  Acknowledgements
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Year : 2000  |  Volume : 48  |  Issue : 1  |  Page : 68-71

Detection of deletion in the dystrophin gene of a patient with quadriceps myopathy.

Human Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.

Correspondence Address:
Human Molecular Genetics Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.

  »  Abstract

A 43 year old male presented with slowly progressive weakness of limbs and hypertrophy of triceps, brachioradialis and calf muscles for four years. There was thinning of quadriceps muscles in both thighs. Histological study was compatible with Becker muscular dystrophy (BMD). Genomic DNA analysis showed a deletion of the Hind III fragments, spanning exons 45-47. A junction fragment of 11.0 kb was observed along with a deletion of a 3.4 kb PstI fragment containing exon 51 in the patient, and in one of his two sisters. The clinical and laboratory characteristics in this patient are in keeping with what has been described 'quadriceps myopathy' and fall within the phenotypic variants of BMD as has been shown by others.

How to cite this article:
Kumari D, Gupta M, Goyle S. Detection of deletion in the dystrophin gene of a patient with quadriceps myopathy. Neurol India 2000;48:68-71

How to cite this URL:
Kumari D, Gupta M, Goyle S. Detection of deletion in the dystrophin gene of a patient with quadriceps myopathy. Neurol India [serial online] 2000 [cited 2021 Jun 18];48:68-71. Available from:

   »   Introduction Top

Many atypical phenotypes of Becker muscular dystrophy (BMD) have been studied since the discovery of the dystrophin gene.[1],[2],[3] Sunohara et al[1] described 4 male patients with quadriceps myopathy (QM), all of whom showed a mild and slowly progressive myopathy confined to quadriceps muscles. They have provided the first evidence that patients with QM have dystrophin abnormalities as seen in BMD. On the other hand, Morandi et al investigated 59 patients for dystrophin expression and genotype but did not come across any case of pure QM.[3] Cartier et al described the clinical and laboratory characteristics of a late focal dystrophy, as a form of muscular dystrophy.[4]
There are few reports of QM being a genetic variant of BMD. We have identified one patient who presented with clinical picture consistent with QM, from about 200 muscular dystrophy patients, who were studied in our laboratory for deletion analysis, in the last five years. He had deletion pattern consistent with BMD, indicating that 'QM' is a form of muscular dystrophy, and an atypical presentation of Becker muscular dystrophy. This is the first report from India.

   »   Materials and methods Top

Case report: VK, a 43 year old male presented with enlargement of calf muscles since adolescence, progressive buckling of knees, difficulty in getting up from squatting position and climbing stairs for the last 4-5 years. He had difficulty in running and had frequent falls since the age of 4 years. He underwent coronary artery bypass surgery three years back. The status of cardiomyopathy could not be ascertained. On examination, he had hypertrophy of triceps, brachioradialis and calf muscles. There was thinning of both thighs, (right more than left). Power in both the upper and lower limbs around hip and knee was 4/5, while, distally at the ankle it was 5/5. Gowers' sign was positive. Deep tendon reflexes were all elicitable. Plantars were flexors. EMG from quadriceps muscle showed a myopathic pattern. ECG was within normal limits and the serum CK was 352 IU/L. Histopathology of the muscle biopsy was consistent with muscular dystrophic pattern. The patient after two years of follow up showed progressive worsening of the weakness. Dystrophin immunochemistry of the muscle biopsy could not be performed. Four sisters and one brother were examined and found to be normal.
Genetic analysis: Peripheral blood was taken from the patient, his brother and two sisters. Genomic DNA was isolated from heparinised blood of the patient and his family members as described earlier.[4] Twenty seven exons of the dystrophin gene were analysed by multiplex polymerase chain reaction (mPCR), using three different multiplex primer sets. Multiplex I and II were performed as described previously.[5],[6] Multiplex III was designed by us, based on the published primer sequences.[4] PCR was set up using reagents from Promega (USA). Digests for cDNA analysis were carried out with HindIII, Taq I, PstI and BglII restriction enzymes and samples were run on 1% agarose gel, (20 to 24 cm in length). DNA was blotted to Hybond N+ membrane (Amersham) and prepared for hybridisation with some modifications.[4] cDMD probes 1-2a, 2b-3, 4-5a, 5b-7, 8, and 9-14 were obtained from the ATCC (USA). cDNA 9-14 was further digested with BamHI to separate probes 9, 10 and 11-14.

   »   Results Top

The biopsied muscle specimen in VK showed marked variation in fibre size, fibre splitting and mild to moderate increase in number of internal nuclei. At places the muscle was replaced by fatty tissue. Mild increase in endomysial and perimysial fibrous connective tissue, occasional grouped fibre regeneration suggested active and chronic myopathy consistent with Becker muscular dystrophy. Group atrophy of fibres indicative of denervation was also observed.
PCR analysis with multiplex Set I and II revealed deletions in VK for exons 45 and 47 respectively [Figure - 1]. Southern blot analysis revealed the deletion of 0.5 kb, 1.5 kb and 10.0 kb HindIII fragments corresponding to exons 45, 46 and 47 of the dystrophin gene [Figure 2A] and [Figure 2B]. There was no exonic deletion in the brother (VKB). Further, Southern blot analysis using 3 more restriction enzymes (TaqI, BglII and PstI) with cDNA 8, detected deletion of exon 47 in VK by the absence of fragments 3.7 kb TaqI, 3.5 kb BglII [Figure - 3] and 5.4 kb PstI [Figure 2C]. In addition, a junction fragment of ~ 11.0 kb was observed along with the deletion of 3.4 kb PstI fragment containing exon 51 [Figure 2C].This junction fragment was also present in one of his sisters (VKSi1), but was absent in the brother (VKB) and one of the other sisters (VKSi2) [Figure 2D]. This indicates that VKSi1 is a carrier of the deletion in her brother.

   »   Discussion Top

After the introduction of dystrophin testing in the evaluation of muscle biopsy, a number of atypical presentations of Xp21 muscular dystrophy have been reported e.g. severe dilating cardiomyopathy, cramps and myalgias, myoglobinuria and quadriceps myopathy.[2],[8],[9],[10],[11]
cDNA analysis identified the deletion of exons 45, 46 and 47 in the present study, a pattern consistent with the inframe deletion pattern of BMD. This deletion pattern is same as reported in other cases of dystrophin deficiency with BMD.[1],[2],[3] Perhaps, the most intriguing observation is the clinical variability exhibited by patients with similar deletion of exons 45-47. Most of them have a fairly slow progression. Beggs et al presented 11 patients with inframe deletion of 45-47, of which four patients had slow progressive myopathy and two carried the diagnosis of quadriceps myopathy.[2] In addition, the deletion of exons 45-48 has also been reported in two QM patients. The deletion of exons 45-47 and 45-48 does not cause a shift in the reading frame, resulting in the synthesis of slightly smaller dystrophin protein. Therefore, one can speculate that the benign clinical course of quadriceps myopathy results from the relatively high quantities of dystrophin.[7] On the basis of the genetic testing, we conclude that this case of quadriceps myopathy is an atypical form of Becker muscular dystrophy.

   »   Acknowledgements Top

A Fellowship to D. Kumari from University Grants Commission, and financial help from Department of Biotechnology and Indian Council of Medical Research, New Delhi is gratefully acknowledged.


  »   References Top

1.Sunohara N, Arahata K, Hoffman EP et al: Quadriceps myopathy: forme fruste of Becker muscular dystrophy, Ann Neurol 1990; 28: 634-639.   Back to cited text no. 1    
2.Beggs AH, Hoffman EP, Snyder JR et al: Exploring the molecular basis for variability among patients with Becker muscular dystrophy: Dystrophin gene and protein studies, Am J Hum Genet 1991; 49: 54-67.   Back to cited text no. 2    
3.Morandi L, More M, Confalonieri V et al: Dystrophin characterisation in BMD patients: correlation of abnormal protein with clinical phenotype, J Neurol Sci 1995; 132: 146-55.   Back to cited text no. 3    
4.Cartier L, Hernandez JE, Stuardo A et al: Quadriceps myopathy: a type of late focal dystrophy in a case (in Spanish), Rev Med Chil 1995; 123: 81-84.   Back to cited text no. 4    
5.Mital A, Kumari D, Gupta M et al: Molecular characterisation of Duchenne muscular dystrophy and phenotypic correlation, J Neurol Sci 1998; 157 (2): 179-86.   Back to cited text no. 5    
6.Beggs AH, Koenig M, Boyce FM et al: Detection of 98% of DMD/BMD deletions by polymerase chain reaction, Hum Genet 1990; 86: 45-48.   Back to cited text no. 6    
7.Chamberlain JS, Gibbs RA, Ranier JE et al: Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification, Nucleic Acids Research 1998; 16: 11141-11156.   Back to cited text no. 7    
8.Palmucci L, Doriguzzi C, Mongini T et al: Dilating cardiomyopathy as the expression of Xp21 Becker type muscular dystrophy, J Neurol Sci 1992; 111: 218-221.   Back to cited text no. 8    
9.Gospe SM, Lazaro RP, Lava NS et al: Familial X-linked myalgia and cramps: a nonprogressive myopathy associated with a deletion in the dystrophin gene, Neurology 1989; 39: 1227-1280.  Back to cited text no. 9    
10.Doriguzzi C, Palmucci L, Mongini T et al: Exercise intolerance and recurrent myogloninuria as the only expression of Xp21 Becker type muscular dystrophy, J Neurol 1993; 240: 269-271.  Back to cited text no. 10    
11.Von-mitzlaff HC, Liechti-Gallati S, Rosler KM et al: Quadriceps myopathy as dystrophin-associated myopathy (in German), Schweiz Med Wochenschr 1993;123: 1865-1869.   Back to cited text no. 11    


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