Clin Genet 1999: 55: 376–380 Printed in Ireland. All rights resered Short Report High frequency of de noo deletions in Mexican Duchenne and Becker muscular dystrophy patients. Implications for genetic counseling Alca ´ntara MA, Villarreal MT, Del Castillo V, Gutie ´rrez G, Saldan ˜a Y, Maulen I, Lee R, Macı ´as M, Orozco L. High frequency of de noo deletions in Mexican Duchenne and Becker muscular dystrophy pa- tients. Implications for genetic counseling. Clin Genet 1999: 55: 376–380. © Munksgaard, 1999 Duchenne muscular dystrophy (DMD) is the most common lethal hereditary neuromuscular disease. As there is no effective treatment, accurate carrier detection is essential for genetic counseling and preven- tion. Although linkage analysis has been widely used for this purpose, being an indirect analysis it has several limitations. Using linkage anal- ysis for carrier detection, we found serious limitations, mainly because 82.9% of all proposita were isolated cases. We used quantitative poly- merase chain reaction for direct carrier detection in families with exon deletions and found a higher than expected frequency of de noo dele- tions (62.2%). Furthermore, only 20.7% of the mothers of isolated dele- tion DMD/Becker muscular dystrophy (BMD) patients were found to be carriers. This result suggests that the Mexican population has a high frequency of de noo DMD mutations. MA Alca ´ ntara a , MT Villarreal a , V Del Castillo a , G Gutie ´ rrez a , Y Saldan ˜a a , I Maulen a , R Lee a , M Macı´as a and L Orozco a,b a Department of Research in Human Genetics, National Institute of Pediatrics, b CICATA-IPN, Mexico City, Mexico Key words: carrier detection – Duchenne muscular dystrophy – gene deletion – quantitative PCR Corresponding author: Lorena Orozco, In- stituto Nacional de Pediatrı ´a, Insurgentes Sur No. 3700-C, Col. Insugentes-Cuicuilco, Del. Coyoaca ´ n, D.F. 04530, Me ´ xico. Fax: +52 5 606 59 81 Received 2 October 1998, revised and ac- cepted for publication 28 January 1999 Duchenne muscular dystrophy (DMD) is the most common lethal neuromuscular genetic disease af- fecting approximately 1/3500 males (1). Both Duchenne and the milder allelic form Becker mus- cular dystrophy (BMD) are inherited as X-linked recessive disorders, caused by mutations of the dystrophin gene located at Xp21 (2). Approxi- mately 50–60% of the affected individuals have a deletion of one or more exons clustered at two hotspots: 30% at the proximal and about 70% at the central region of the gene; and approximately 6% of the patients have exon duplications (3–7). The frequency and distribution of deletions and duplications apparently show no ethnic variance (8); however, this issue has been a matter of con- troversy (9 – 15). So far, there is no effective treatment for the disease. Therefore, determination of carrier status is of utmost importance for genetic counseling and prevention. Although linkage analysis is a common approach for carrier detection, there is a high recombination rate across the gene (12%) (16), and the non-carrier state of mothers of iso- lated cases can only be determined if they are heterozygous for an intradeletion polymorphism. Other techniques such as quantitative Southern blot and multiplex quantitative polymerase chain reaction (MQ-PCR) have been successfully used to quantify gene dosage for the direct identifica- tion of gene deletion/duplication carriers (15, 17 – 19); and variations of quantitative PCR have been thoroughly assessed indicating that the technique may completely discriminate between deletion car- riers and normal females (20). We studied the frequency and distribution of exon deletions in 76 Mexican DMD/BMD pa- tients, and used the quantitative PCR procedure described by Abbs and Bobrow (17) for carrier detection, finding a high frequency of de noo deletions. 376