COMPARISON OF SERUM CREATINE KINASE ESTIMATION WITH SHORT TANDEM REPEATS BASED LINKAGE ANALYSIS IN CARRIERS AND AFFECTED CHILDREN OF DUCHENNE MUSCULAR DYSTROPHY
Abstract
Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive lethal, genetic disordercharacterised by progressive weakness of skeletal muscles which is untreatable and transmitted to malesby carrier females. Advances in laboratory techniques now focus direct mutational analysis as the mostreliable 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 studywas 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 DMDwho were referred from different hospitals for evaluation/workup of DMD. SCK was done as apreliminary investigation in all index cases. The PCR assay with STR based linkage analysis with Intron44, 45, 49 and 50 of DMD gene were performed in all families. Six families were informative withIntron 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 informativefamilies. SCK was not performed on Chorionic villous sample (CVS) done for prenatal diagnosis ofDMD, and CVS and non-informative family members were excluded from the study. Results: Incarriers of DMD, the sensitivity and negative predictive value of SCK were 33.3%, and specificity andpositive predictive were 100% with diagnostic efficiency of 50%. In affected cases of DMD thesensitivity and negative predictive value of SCK were 100%, and specificity and positive predictive were91% and 88.8% respectively and diagnostic efficiency of 94.1%. Conclusion: The SCK is an excellentscreening test for affected cases of DMD. For carrier identification we have to resort on PCR analysis soas to provide safer diagnostic tool for genetic counselling and prenatal diagnosis.Keywords: Duchenne muscular dystrophy, Creatine Kinase, Carrier detection, Short Tandem RepeatsReferences
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.
–538.
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;
p.2206–10.
Biggar WD. Duchenne muscular dystrophy. Pediatr Rev
;27:83–8.
Prior TW, Bridgeman SJ. Experience and strategy for the
molecular testing of Duchenne muscular dystrophy. J Mol Diagn
;7:317–26.
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
;21:567–70.
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
;62:511–20.
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
;74:550–3.
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
;49:951–60.
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
;40:635–42
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.
Published
Issue
Section
License
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.
