Rizwan Hashim, Sajida Shaheen, Suhaib Ahmad, Abdus Sattar, Farooq Ahmad Khan


Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive lethal, genetic disorder
characterised by progressive weakness of skeletal muscles which is untreatable and transmitted to males
by carrier females. Advances in laboratory techniques now focus direct mutational analysis as the most
reliable and indirect analysis based on Short Tandem Repeats (STR) based linkage analysis as feasible,
inexpensive, and efficient method for carrier detection and prenatal diagnosis. The objective of this study
was to compare the sensitivity, specificity, positive predictive value (PPV), negative predictive value
(NPV) and diagnostic efficiency of Serum Creatine Kinase (SCK) with Short Tandem Repeats (STR)
based linkage analysis in carriers and affected children of Duchenne Muscular Dystrophy. Methods:
The study was carried out from Dec 2006 to Dec 2007 in families having index clinical cases of DMD
who were referred from different hospitals for evaluation/workup of DMD. SCK was done as a
preliminary investigation in all index cases. The PCR assay with STR based linkage analysis with Intron
44, 45, 49 and 50 of DMD gene were performed in all families. Six families were informative with
Intron 44 of DMD gene and one family was non-informative with all four intronic markers of DMD.
SCK analyses were done in all the family members and compared with PCR analysis in informative
families. SCK was not performed on Chorionic villous sample (CVS) done for prenatal diagnosis of
DMD, and CVS and non-informative family members were excluded from the study. Results: In
carriers of DMD, the sensitivity and negative predictive value of SCK were 33.3%, and specificity and
positive predictive were 100% with diagnostic efficiency of 50%. In affected cases of DMD the
sensitivity and negative predictive value of SCK were 100%, and specificity and positive predictive were
91% and 88.8% respectively and diagnostic efficiency of 94.1%. Conclusion: The SCK is an excellent
screening test for affected cases of DMD. For carrier identification we have to resort on PCR analysis so
as to provide safer diagnostic tool for genetic counselling and prenatal diagnosis.
Keywords: Duchenne muscular dystrophy, Creatine Kinase, Carrier detection, Short Tandem Repeats

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Jones CLV. Inherited diseases. In: Burtis CA, Ashwood ER,

Bruns DE, (editors). Teitz text book of clinical chemistry and

Molecular Diagnostics. 4th ed. New Dehli: Elsevier; 2006.p.


Barohn RJ. Muscular dystrophies. In: Drazen JM, Gill GN,

Griggs RC, Kokko JP, Mandell GL, Powell DW, (editors). Cecil

textbook of medicine. 21st edition. Philadelphia: WB Saunders;


Biggar WD. Duchenne muscular dystrophy. Pediatr Rev


Prior TW, Bridgeman SJ. Experience and strategy for the

molecular testing of Duchenne muscular dystrophy. J Mol Diagn


Sarnat MB. Neuromuscular disorders. In: Behrman RE,

Kliegman RM, Jensen HB, (editors). Nelson Textbook of

Pediatrics. 17th ed. Philadelphia: WB Saunders; 2004.p. 2053–82.

Roberts RG. Dystrophin, its gene and dystrophinopathies. Adv

Genet 1995;33:177–231.

Hauser MA, Chamberlain JS. Progress towards gene therapy for

Duchenne muscular dystrophy. J Endocrinol 1996;149:373–8.

Chakraborty R, Zhong Y, Andrade M, Clemens PR, Fenwick

RG, Caskey CT. Linkage disequilibria among (CA)n

Polymorphisms in the human dystrophin gene and their

implications in carrier detection and prenatal diagnosis in

Duchenne and Becker muscular dystrophies. Genomics


Bachrati CZ, Somodi Z, Endreffy E, Kalmar T and Rasko I.

Carrier detection by microsatellite analysis of Duchenne/Becker

muscular dystrophy in Hungarian families. Ann Human Genet


Katirji B, Al-Jaberi MM. Creatine kinase revisited. J Clin

Neuromus Dis 2001;2:158–63.

Parsons E, Bradley D, Clarke A. Disclosure of Duchenne

muscular dystrophy after new born screening. Arch Dis Child


Lott JA, Landesman PW. The enzymology of skeletal muscle

disorders. Crit Rev Clin Lab Sci 1984;20:153–90.

Moser H. Duchenne muscular dystrophy: pathogenetic aspects

and genetic prevention. Hum Genet 1984;66:17–40.

Ahmad S. Practical demonstration in molecular genetics. In:

Ahmad S, Ikram N, Ayyub M, Shamsi T, Kakepoto GN, Zafar T,

(editors). Book of abstracts: first national conference and 4th post

graduate course in haematology; Oct 2–4 1998; Rawalpindi:

p. 31–6.

Clemens PR, Fenwick RG, Chamberlain JS, Gibbs RA, Andrade

M, Chakraborty R. Carrier detection and prenatal diagnosis in

Duchenne and Becker muscular dystrophy families, using

dinucleotide repeat polymorphisms. Am J Hum Genet


Schumann G, Bonora R, Ceriotti F, Clerc–Renaud P, Fererd G,

Ferrero CA, et al. IFCC primary reference procedures for the

measurement of catalytic activity concentrations of enzymes at

°C. Part 2. Reference procedures for the measurement of

catalytic concentration of creatine Kinase. Clin Chem Lab Med


Arahata K. Dystrophin abnormality in progressive muscular

dystrophy - a review article. Acta Paediatr Jpn 1991;33:216–21.

Feener CA, Boyce FM, Kunkel LM. Rapid detection of CA

polymorphisms in cloned DNA: application to the 5´ region of

the dystrophin gene. Am J Hum Genet 1991;48:621–7.

Khan MA, Ali AS, Rind A, Hassan F, Haque SU. Results of

muscle biopsies from cases of progressive muscular weakness.

Pak J Pathol 1998;9:121–3.

Ohta M, Itagak Y, Itoh N, Hayashi K, Nishitani K, Ohta K.

Carbonic anhydrase III in serum in muscular dystrophy and other

neurological disorders: relationship with creatine kinase. Clin

Chem 1991;37:36–9.

Dellamonica C, Collombel C, Cotte J, Addis P. Screening for

neonatal Duchenne muscular dystrophy by bioluminescence

measurement of creatine kinase in a blood sample spotted on

paper. Clin Chem 1983;29:161–3.


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