Brief Clinical Report Double Missense Mutation in Exon 41 of the Human Dystrophin Gene Detected by Double Strand Conformation Analysis Fawzy A. Saad, 1,2 * Luciano Merlini, 3 Maria Luisa Mostacciuolo, 1 and Gian Antonio Danieli 1 1 Department of Biology, University of Padua, Padua, Italy 2 Department of Genetics, University of Tanta, Kafr El Sheikh, Egypt 3 Neuromuscular Laboratory, Rizzoli Institute, University of Bologna, Bologna, Italy Development of late-onset Becker muscular dystrophy is reported in a patient whose two healthy brothers showed high serum creatine kinase level. No cases of neuromus- cular disorders had been previously re- ported in this family. The analysis of the dystrophin gene showed that the three brothers had A → C transversion at nucleo- tide 6092 in exon 41, a missense mutation which converts lysine into glutamine. The symptomatic patient showed an additional mutation in the same exon, a T → C transi- tion at nucleotide 6119, converting a phenyl- alanine to leucine. The possible pathogenic role of this mutation is discussed. Am. J. Med. Genet. 80:99–102, 1998. © 1998 Wiley-Liss, Inc. KEY WORDS: dystrophin; double mutation; missense; DSCA INTRODUCTION Screening for point mutations of the dystrophin gene is widely used for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) pa- tients who show no intragenic alteration of the gene. However, the occurrence of dystrophinopathies with variant clinical expression [Gospe et al., 1989; Bushby et al., 1991; Servidei et al., 1993; Heald et al., 1994; Palmucci et al., 1994] suggests that screening of all dystrophinopathies for dystrophin gene point muta- tions may be of considerable clinical value. The present report deals with a patient manifesting late-onset Becker muscular dystrophy, in whom mutation screen- ing was motivated by detection of unusually high se- rum creatine kinase (CK) levels in the patient’s two apparently healthy brothers. CLINICAL REPORT A 62-year-old Italian man was admitted with marked muscle impairment of limb girdle motor func- tion. Lower limb weakness began at age 55. He expe- rienced increasing difficulty in running, raising him- self from the floor, and climbing stairs. Six years later he was admitted to the local hospital and found to have an abnormally high serum CK level. The patient was treated with steroids for a few months, without any noticeable improvement of his clinical conditions. Therefore, at age 62 the patient was referred to a spe- cialized center for further investigation. On examination, he was slender without calf hyper- trophy. Manual muscle testing demonstrated very mild weakness of the deltoids (MRC 5-), overt involvement of the biceps (MRC 4-), and of the finger extensors (MRC 3-). Pelvic girdle muscles were also involved (MRC 4-), while quadricep and abdominal muscle strength was graded at MRC 4. The quadriceps peak torque values, recorded at 30 degrees/sec [Merlini et al., 1992], were 65 Nm on the right and 90 Nm on the left (normal mean value, 200 Nm). The hamstring peak torque values were 68 and 78 Nm respectively (normal mean value, 119 Nm). Achilles tendon reflexes were absent. Muscle ultrasound imaging showed strikingly dif- fuse echo increase in the quadriceps. Electromyogra- phy (EMG) demonstrated a myopathic pattern in the biceps with many brief (and occasionally polyphasic) motor unit potentials. Muscle computed tomographic scan showed mild and diffuse muscle hypotrophy with focal rounded areas of low density in the thigh muscles and in the glutei. Contract grant sponsor: Telethon; Contract grant sponsor: Ital- ian Ministry of Foreign Affairs. *Current address of F.A.S. is Department of Medicine, Univer- sity of Toronto, 67 College Street, Toronto, Ontario M5G 2M1 Canada. E-mail: fawzy.saad@utoronto.ca *Correspondence to: Fawzy A. Saad, Ph.D., University of Padua, Via Trieste 75, I-35121 Padova, Italy. Received 5 October 1996; Accepted 21 July 1998 American Journal of Medical Genetics 80:99–102 (1998) © 1998 Wiley-Liss, Inc.