Detection of Duchenne/Becker Muscular Dystrophy Carriers in a Group of Iranian Families by Linkage Analysis
This study determines the value of linkage analysis using six RFLP markers for carrier detection and prenatal diagnosis in familial DMD/BMD cases and their family members for the first time in the Iranian population. We studied the dystrophin gene in 33 unrelated patients with clinical diagnosis of DMD or BMD. Subsequently, we determined the rate of heterozygosity for six intragenic RFLP markers in the mothers of patients with dystrophin gene deletions. Finally, we studied the efficiency of linkage analysis by using RFLP markers for carrier status detection of DMD/BMD. In 63.6% of the patients we found one or more deletions. The most common heterozygous RFLP marker with 57.1% heterozygosity was pERT87.15Taq1. More than 80% of mothers in two groups of familial or non-familial cases had at least two heterozygous markers. Family linkage analysis was informative in more than 80% of the cases, allowing for accurate carrier detection. We found that linkage analysis using these six RFLP markers for carrier detection and prenatal diagnosis is a rapid, easy, reliable, and inexpensive method, suitable for most routine diagnostic services. The heterozygosity frequency of these markers is high enough in the Iranian population to allow carrier detection and prenatal diagnosis of DMD/BMD in more than 80% of familial cases in Iran.
Emery AE. The muscular dystrophies. Lancet 2002;359(9307):687-95.
Blyth H, Pugh RJ. Muscular dystrophy in childhood; the genetic aspect; a field study in the Leeds region of clinical types and their inheritance. Ann Hum Genet 1959;23(2):127-63.
Worton R. Muscular dystrophies: diseases of the dystrophin-glycoprotein complex. Science 1995;270(5237):755-6.
Den Dunnen JT, Grootscholten PM, Bakker E, Blonden LA, Ginjaar HB, Wapenaar MC, van Paassen HM, van Broeckhoven C, Pearson PL, van Ommen GJ. Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. Am J Hum Genet 1989;45(6):835-47.
Hu XY, Burghes AH, Ray PN, Thompson MW, Murphy EG, Worton RG. Partial gene duplication in Duchenne and Becker muscular dystrophies. J Med Genet 1988;25(6):369-76.
Beggs AH, Koenig M, Boyce FM, Kunkel LM. Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 1990;86(1):45-8.
Laing NG. Molecular genetics and genetic counselling for Duchenne/Becker muscular dystrophy. Mol Cell Biol Hum Dis Ser 1993;3:37-84. Review.
Bakker E, Hofker MH, Goor N, Mandel JL, Wrogemann K, Davies KE, Kunkel LM, Willard HF, Fenton WA, Sandkuyl L, et al. Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs. Lancet 1985;1(8430):655-8.
Ligon AH, Kashork CD, Richards CS, Shaffer LG. Identification of female carriers for Duchenne and Becker muscular dystrophies using a FISH-based approach. Eur J Hum Genet 2000;8(4):293-8.
Gatta V, Scarciolla O, Gaspari AR, Palka C, De Angelis MV, Di Muzio A, Guanciali-Franchi P, Calabrese G, Uncini A, Stuppia L. Identification of deletions and duplications of the DMD gene in affected males and carrier females by multiple ligation probe amplification (MLPA). Hum Genet 2005;117(1):92-8. Epub 2005 Apr20.
Abbs S, Bobrow M. Analysis of quantitative PCR for the diagnosis of deletion and duplication carriers in the dystrophin gene. J Med Genet 1992;29(3):191-6.
Joncourt F, Neuhaus B, Jostarndt-Foegen K, Kleinle S,Steiner B, Gallati S. Rapid identification of female carriersof DMD/BMD by quantitative real-time PCR. Hum Mutat 2004;23(4):385-91.
Clemens PR, Fenwick RG, Chamberlain JS, Gibbs RA, de Andrade M, Chakraborty R, Caskey CT. Carrier detection and prenatal diagnosis in Duchenne and Becker musculardystrophy families, using dinucleotide repeat polymorphisms. Am J Hum Genet 1991;49(5):951-60.
Darras BT, Harper JF, Francke U. Prenatal diagnosis and detection of carriers with DNA probes in Duchenne's muscular dystrophy. N Engl J Med 1987;316(16):985-92.
Lindlöf M, Kääriäinen H, Davies KE, de la Chapelle A.Carrier detection and prenatal diagnosis in X linked muscular dystrophy using restriction fragment lengthpolymorphisms. J Med Genet 1986;23(6):560-72. Erratumin: J Med Genet 1987;24(3):171.
Roberts RG, Cole CG, Hart KA, Bobrow M, Bentley DR.Rapid carrier and prenatal diagnosis of Duchenne and Becker muscular dystrophy. Nucleic Acids Res 1989;17(2):811.
Miller SA, Dykes DD, Polesky HF. A simple salting outprocedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16(3):1215.
Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN,Caskey CT. Deletion screening of the Duchenne musculardystrophy locus via multiplex DNA amplification. Nucleic Acids Res 1988;16(23):11141-56.
Roberts RG, Bobrow M, Bentley DR. A MaeIII polymorphism near the dystrophin gene promoter by restriction of amplified DNA. Nucleic Acids Res1990;18(5):1315.
Roberts RG, Barby TF, Manners E, Bobrow M, Bentley DR. Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes. Am J Hum Genet 1991;49(2):298-310.
Abbs S, Roberts RG, Mathew CG, Bentley DR, Bobrow M. Accurate assessment of intragenic recombination frequency within the Duchenne muscular dystrophy gene. Genomics 1990;7(4):602-6.
González-Herrera L, Gamas-Trujillo PA, García-Escalante MG, Castillo-Zapata I, Pinto-Escalante D. Identifying deletions in the dystrophin gene and detecting carriers in families with Duchenne's/Becker's muscular dystrophy. Rev Neurol 2009;48(2):66-70.
Alcántara Ortigoza MA, Aguinaga Ríos M, González del Angel A, Zavaleta Abreu Mde J, Acevedo Gallegos S, Mayén Molina DG, del Castillo Ruíz V. Prenatal molecular diagnosis of a DMD carrier female fetus by chorionic villus sampling and linkage analysis. Ginecol Obstet Mex 2009;77(2):103-9.
Percesepe A, Ferrari M, Coviello D, Zanussi M, Castagni M, Neri I, Travi M, Forabosco A, Tedeschi S. Detection of a novel dystrophin gene mutation through carrier analysis performed during prenatal diagnosis in a case with intragenic recombination. Prenat Diagn 2005;25(11):1011-4.
Sacare VK. Molecular genetic characteristics of Duchenne-Becker muscular dystrophy in the Republic of Moldova. Genetika 2008;44(10):1404-9.
Yau SC, Roberts RG, Bentley DR, Mathew CG, Bobrow M. A MseI polymorphism in exon 48 of the dystrophingene. Nucleic Acids Res 1991;19(20):5803.