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Duchenne Muscular Dystrophy (DMD) is a severe X-linked recessive disorder characterized by progressive muscle degeneration due to dystrophin deficiency. Cardiac involvement, particularly dilated cardiomyopathy, significantly impacts morbidity and mortality, typically manifesting after age 10. This case report presents a rare instance of early-onset cardiac involvement in a 3-year-old male with a confirmed deletion in exon 55 of the dystrophin gene. The patient developed dilated cardiomyopathy at 3 years and 8 months, with progressive left ventricular dysfunction despite early treatment with corticosteroids, ACE inhibitors, and beta-blockers. Genetic mechanisms and genotype–phenotype correlations related to cardiac involvement were reviewed, highlighting emerging therapies such as exon skipping, vamorolone, ifetroban, and rimeporide. Studies indicate that variants in exons 12, 14–17, 31–42, 45, and 48–49 are associated with more severe cardiac impairment. This case emphasizes the need for early, ongoing cardiac assessment and personalized treatment to address disease heterogeneity. While current DMD care standards improve survival, optimizing management through early intervention and novel therapies remains essential. Further research is needed to better understand genotype–phenotype correlations and improve cardiac outcomes for patients with DMD. [ABSTRACT FROM AUTHOR]

Objectives: To assess the clinical and molecular profile of patients with Duchenne Muscular Dystrophy (DMD) presenting to a tertiary center in Eastern Region of Uttar Pradesh, India. Methods: In this retrospective study, case records of all patients diagnosed as DMD were analyzed to ascertain the clinical phenotype and molecular profile. Multiplex polymerase chain reaction (mPCR) technique, Multiplex Ligation Dependent Probe Amplification (MLPA) and Next Generation Sequencing (NGS) were used for establishing the molecular diagnosis. Leiden Open Variation Database (LOVD) frame checker online tool was used to predict clinical severity of the cases. Results: Records of 112 children with DMD were analyzed. The median (IQR) age of onset and clinical presentation of disease was 60 (12, 132) months and 90 (33, 156) months, respectively. The most common clinical presentations were difficulty in standing from sitting position (n = 107), difficulty in climbing stairs (n = 106), and difficulty in walking (n = 99). Bilateral calf muscle hypertrophy and a positive Gower's sign was seen in 110 and 108 patients at presentation. The median (IQR) creatinine phosphokinase (CPK) levels at diagnosis were 6296.5 (4320, 7432.5) U/L. The genetic variation in 111 patients were reported as deletion (n = 105), duplication (n = 3), and point variation (n = 3). 22 patients could benefit from the available exon skipping therapy. Exondys (exon 51 skipping) could be used in 14 patients. Conclusion: Deletions were recorded in a much higher proportion of patients compared to previous studies from India. There were 22 patients who could have been benefitted by the available exon skipping therapy. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle degenerative disease caused by mutations in the dystrophin gene, resulting in death by the end of the third decade of life at the latest. A key aspect of the DMD clinical phenotype is dilated cardiomyopathy, affecting virtually all patients by the end of the second decade of life. Furthermore, despite respiratory complications still being the leading cause of death, with advancements in medical care in recent years, cardiac involvement has become an increasing cause of mortality. Over the years, extensive research has been conducted using different DMD animal models, including the mdx mouse. While these models present certain important similarities to human DMD patients, they also have some differences which pose a challenge to researchers. The development of somatic cell reprograming technology has enabled generation of human induced pluripotent stem cells (hiPSCs) which can be differentiated into different cell types. This technology provides a potentially endless pool of human cells for research. Furthermore, hiPSCs can be generated from patients, thus providing patient-specific cells and enabling research tailored to different mutations. DMD cardiac involvement has been shown in animal models to include changes in gene expression of different proteins, abnormal cellular Ca2+ handling, and other aberrations. To gain a better understanding of the disease mechanisms, it is imperative to validate these findings in human cells. Furthermore, with the recent advancements in gene-editing technology, hiPSCs provide a valuable platform for research and development of new therapies including the possibility of regenerative medicine. In this article, we review the DMD cardiac-related research performed so far using human hiPSCs-derived cardiomyocytes (hiPSC-CMs) carrying DMD mutations. [ABSTRACT FROM AUTHOR]

Background: Methodological advancements, such as relative haplotype and relative mutation dosage analyses, have enabled non-invasive prenatal diagnosis of autosomal recessive and X-linked diseases. Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive proximal muscular dystrophy and a high mortality rate before the age of twenty. We aimed to systematically present obtainable data regarding a non-invasive prenatal diagnosis of DMD and provide a comprehensive resume on the topic. The emphasis was given to the comparison of different available protocols and molecular methods used for fetal inheritance deduction, as well as their correlation with prognostic accuracy. Methods: We searched the Scopus and PubMed databases on 11 November 2022 and included articles reporting a non-invasive prenatal diagnosis of DMD in families at risk using relative dosage analysis methods. Results: Of the 342 articles identified, 7 met the criteria. The reported accuracy of NIPT for DMD was 100% in all of the studies except one, which demonstrated an accuracy of 86.67%. The combined accuracy for studies applying indirect RHDO, direct RHDO, and RMD approaches were 94.74%, 100%, and 100%, respectively. Confirmatory results by invasive testing were available in all the cases. Regardless of the technological complexity and low prevalence of the disease that reduces the opportunity for systematic research, the presented work demonstrates substantial accuracy of NIPT for DMD. Conclusions: Attempts for its implementation into everyday clinical practice raise many ethical and social concerns. It is essential to provide detailed guidelines and arrange genetic counseling in order to ensure the proper indications for testing and obtain informed parental consent. [ABSTRACT FROM AUTHOR]

Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive muscular dystrophy that affects young boys and is caused by mutation of the dystrophin gene located over X chromosome. Materials and Methods: In this prospective study, 120 clinically diagnosed DMD patients were tested for exon deletions, duplication or point mutation. Results: Of the 120 clinically suspected DMD patients, the diagnosis of DMD was confirmed by the genetic study or muscle biopsy in 116 patients. The mean age of onset was 3.2 years and the mean age at presentation was 7.2 years. 110/120 cases were confirmed by genetic testing and six were by absence of staining for dystrophin on muscle biopsy. DMD gene deletion was present in 78.5%, duplication in 5.3% and point mutation in 11.2% cases. 70.3% of patients had deletion located at a distal hot spot region. Single exon deletion was found in 16.5%. Distal hotspot exons 47, 48 and 50 were the commonly deleted exons. Conclusions: In our study, 94.8% cases showed genetic change in the DMD gene. Muscle biopsy was the choice of investigation in earlier days. Detection of DMD by DNA based method eliminates the need to do an invasive procedure for diagnosis. Hence the genetic testing should be the investigation of choice in suspected cases of DMD. The pattern of deletion, obtained in the population of Rajasthan was similar when compared with other ethnic groups of the Indian population. It would be helpful for researchers to develop drugs specific to exons or for ongoing mutation-specific therapies.

Abstracts Background Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. Methods We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. Results We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. Conclusions We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD.

Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive muscular dystrophy that affects young boys and is caused by mutation of the dystrophin gene located over X chromosome. Materials and Methods: In this prospective study, 120 clinically diagnosed DMD patients were tested for exon deletions, duplication or point mutation. Results: Of the 120 clinically suspected DMD patients, the diagnosis of DMD was confirmed by the genetic study or muscle biopsy in 116 patients. The mean age of onset was 3.2 years and the mean age at presentation was 7.2 years. 110/120 cases were confirmed by genetic testing and six were by absence of staining for dystrophin on muscle biopsy. DMD gene deletion was present in 78.5%, duplication in 5.3% and point mutation in 11.2% cases. 70.3% of patients had deletion located at a distal hot spot region. Single exon deletion was found in 16.5%. Distal hotspot exons 47, 48 and 50 were the commonly deleted exons. Conclusions: In our study, 94.8% cases showed genetic change in the DMD gene. Muscle biopsy was the choice of investigation in earlier days. Detection of DMD by DNA based method eliminates the need to do an invasive procedure for diagnosis. Hence the genetic testing should be the investigation of choice in suspected cases of DMD. The pattern of deletion, obtained in the population of Rajasthan was similar when compared with other ethnic groups of the Indian population. It would be helpful for researchers to develop drugs specific to exons or for ongoing mutation-specific therapies. [ABSTRACT FROM AUTHOR]

Abstract Background Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disorder. Patients with DMD usually have severe and fatal symptoms, including progressive irreversible muscle weakness and atrophy complicated with gastrocnemius muscle pseudohypertrophy. DMD is caused by mutations in the dystrophin-encoding DMD gene, including large rearrangements and point mutations. This retrospective study was aimed at supplying information on our 4-year clinical experience of DMD genetic and prenatal diagnosis at the Department of Prenatal Diagnosis in Women’s Hospital of Nanjing Medical University. Methods Multiplex ligation-dependent probe amplification (MLPA) was used to detect the exon deletions or duplications. And Ion AmpliSeq™ panel for inherited disease was used as the next-generation sequencing (NGS) method to identify the point mutations in exons of DMD gene, but the introns were not sequenced. Results In this study, the large deletions and duplications of DMD gene were detected in 32 (51.6%) of the 62 families, while point mutations were detected in 20 families (32.3%). The remaining 10 families with a negative genetic diagnosis need to be reevaluated for clinical symptoms or be detected by other molecular methods. Notably, six novel mutations were identified, including c.412A > T(p.Lys138*), c.2962delT(p.Ser988Leufs*16), c.6850dupA (p.Ser2284Lysfs*7), c.5139dupA (p.Glu 1714Argfs*5), c.6201_6203delGCCins CCCA(p.Val2069Cysfs*14) and c.10705A > T (p.Lys3569*). In 52 families with positive results, 45 mothers (86.5%) showed positive results during carrier testing and de novo mutations arose in 7 probands. The prenatal diagnosis was offered to 34 fetuses whether the pregnant mother was a carrier or not. As a result, eight male fetuses were affected, three female fetuses were carriers, and the remaining fetuses had no pathogenic mutation. Conclusions This study reported that MLPA and NGS could be used for screening the DMD gene mutations. Furthermore, the stepwise procedure of prenatal diagnosis of DMD gene was shown in our study, which is important for assessing the mutation type of fetuses and providing perinatal care in DMD high-risk families.

Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive diseases caused by mutations in the dystrophin (DMD) gene. To our knowledge, molecular analysis to differentiate between DMD and BMD has never been performed in Indonesia. Objective To elaborate the clinicopathologic and molecular profiles of DMD/BMD patients in Yogyakarta, Indonesia. Methods Eighteen muscle biopsy specimens of patients clinically suspected to have DMD/BMD were collected. Possible associations of clinical manifestations, histopathological grading, and immunohistochemistry (IHC) results were analyzed. Polymerase chain reaction (PCR) was performed to identify mutations in exon 52. Results. Positive Gower’s sign and high serum creatine kinase (CK) were observed in most patients. The IHC of dystrophin in two female patients suggested that they were manifesting carriers. Of the 16 male patients, 12 showed negative IHC staining, indicating DMD, while 4 patients demonstrated weak expression of dystrophin, indicating BMD. There was a significant association between high CK level and IHC results (P=0.005), indicating higher CK level in DMD patients. Histopathological grading of muscle biopsy was significantly associated with diagnosis of DMD/BMD using IHC (P=0.01), showing more severe tissue damage in DMD patients. None of the subjects had the single exon 52 deletion. Conclusion This is the first report of a clinicopathologic and molecular profile of DMD/BMD in an Indonesian population. Serum CK level and histopathological grading of muscle biopsy are useful in distinguishing DMD from BMD in settings where an IHC assay is not available.

Abstract Background In individuals with Duchenne muscular dystrophy (DMD), exon skipping treatment to restore a wild-type phenotype or correct the frame shift of the mRNA transcript of the dystrophin (DMD) gene are mutation-specific. To explore the molecular characterization of DMD rearrangements and predict the reading frame, we simultaneously screened all 79 DMD gene exons of 45 unrelated male DMD patients using a multiplex ligation-dependent probe amplification (MLPA) assay for deletion/duplication patterns. Multiplex PCR was used to confirm single deletions detected by the MLPA. Results There was an obvious diagnostic delay, with an extremely statistically significant difference between the age at initial symptoms and the age of clinical evaluation of DMD cases (t value, 10.3; 95% confidence interval 5.95–8.80, P

Duchenne and Becker muscular dystrophy (DMD/BMD) are the most common neuromuscular diseases caused by mutations in the dystrophin gene also called (DMD gene), located at Xp21. We report the clinical and genetic analysis of 74Algerian DMD/BMD patients from 62unrelated families who attended the neuromuscular unit of the University Hospital Center of Constantine between 2014 and 2017. After informed consent, multiplex polymerase chain reaction (mPCR)was established to identify deletions. All patients presented a classical phenotype dominated by a bilateral and symmetrical motor deficit predominantly proximal with calf hypertrophy in 91.6% of patients, with very high serum CK levels. Molecular analysis of the DMD gene showed, large deletions at all patients. Most of the deletions were between exons 44 and 53, the most frequent were deletions of exons 45-48, with exon 45 as the most common single exon deletion. Our study had generated considerable data on deletions that may promote future experimental therapies in Algeria. [ABSTRACT FROM AUTHOR]

Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive diseases caused by mutations in the dystrophin (DMD) gene. To our knowledge, molecular analysis to differentiate between DMD and BMD has never been performed in Indonesia. Objective To elaborate the clinicopathologic and molecular profiles of DMD/BMD patients in Yogyakarta, Indonesia. Methods Eighteen muscle biopsy specimens of patients clinically suspected to have DMD/BMD were collected. Possible associations of clinical manifestations, histopathological grading, and immunohistochemistry (IHC) results were analyzed. Polymerase chain reaction (PCR) was performed to identify mutations in exon 52. Results Positive Gower's sign and high serum creatine kinase (CK) were observed in most patients. The IHC of dystrophin in two female patients suggested that they were manifesting carriers. Of the 16 male patients, 12 showed negative IHC staining, indicating DMD, while 4 patients demonstrated weak expression of dystrophin, indicating BMD. There was a significant association between high CK level and IHC results (P=0.005), indicating higher CK level in DMD patients. Histopathological grading of muscle biopsy was significantly associated with diagnosis of DMD/BMD using IHC (P=0.01), showing more severe tissue damage in DMD patients. None of the subjects had the single exon 52 deletion. Conclusion This is the first report of a clinicopathologic and molecular profile of DMD/BMD in an Indonesian population. Serum CK level and histopathological grading of muscle biopsy are useful in distinguishing DMD from BMD in settings where an IHC assay is not available. [ABSTRACT FROM AUTHOR]

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Introduction: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are inherited X-linked recessive genetic disorders caused by defects in the dystrophin gene. Abnormality in the dystrophin protein causes progressive muscle damage and weakness leading to long-term disability. Objective: To investigate the spectrum of dystrophin gene variants (deletions and duplications) in Pakistani patients suspected of having DMD/BMD or of being DMD/BMD carriers. Methods: A single center (Aga Khan University Hospital, Karachi, Pakistan) retrospective review of 46 cases was conducted to characterize dystrophin gene variants (deletion/duplication) in DMB/BMD patients using the multiplex ligation-dependent probe amplification-based method to provide coverage for all 79 exons. Results: Dystrophin gene deletions were identified in 40 of 46 cases, whereas duplications were present in 6 of 46 cases. The majority of the deletions were present between exons 45 and 52 followed by the region between exons 8 and 18. The most frequently deleted was exon 46 (8%) followed by exon 49 (7%). Dystrophin gene duplications were clustered between exons 3 and 7. The average deletion or duplication size was five exons for both kinds of variants. Conclusions: The applicability of exon skipping drugs depends on the specific mutational frequencies within populations. Our data suggest that for the Pakistani patients, multiple exon skipping between exons 46 and 49 could potentially be a target for exon skipping therapy. However, a larger nationwide study is required to further identify the predominant deletion/duplication dystrophin gene variants present in the population. [ABSTRACT FROM AUTHOR]

Abstract Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive, inherited neuromuscular disorders, caused by pathogenic variants in the dystrophin gene that encodes the dystrophin protein. A number of mutations have been identified in the past years, producing dystrophin diversity and resulting in mild to severe phenotypes in patients. Mutations in the dystrophin gene can be characterized by laboratory testing to confirm a clinical diagnosis of DMD/BMD. Traditional genetic diagnostic strategy for DMD/BMD involves the initial detection of large mutations, followed by the detection of smaller mutations, where two or more analytical methods are employed. With the development of next generation sequencing (NGS) technology, comprehensive mutational screening for all variant types can be performed on a single platform in patients and carriers, although further optimization and validation are required. Furthermore, the discovery of cell-free fetal DNA (cffDNA) in maternal plasma provides basis for noninvasive prenatal diagnosis of DMD/BMD. Here, we discuss the correlation between genotype and phenotype, the current methods of molecular genetic testing and genetic diagnostic strategy for probands and female carriers of DMD/BMD, the diagnostic ability of a comprehensive targeted NGS strategy and the possibility of it replacing conventional methods. Highlights • The genetic diagnosis for dystrophinopathies is important for proband and family. • With the development of NGS, genetic diagnosis strategy for dystrophinopathies is changing. • There exist advantages and limitations of targeted NGS for genetic testing of dystrophinopathies. • Clinical indications of noninvasive prenatal tests diagnosis based-on NGS for dystrophinopathies is possible. [ABSTRACT FROM AUTHOR]

Direct DNA diagnostics was performed for 91 patients with DMD/B from 81 families, 84 (92.3%) patients with Duchenne muscular dystrophy, 7 (8.6%) patients with Becker muscular dystrophy. The analysis was carried out on 20 exons of the dystrophin gene -- the promoter region, 3, 4, 6, 8, 13, 17, 19, 32, 42, 43, 44, 45, 47, 48, 50, 51, 52, 53, 60 exons. Indirect diagnosis was carried out in 21 families burdened with DMD/B using intragenic highly polymorphic markers located in the 45th (STR-45), 49th (STR-49), 50th (STR-50) gene introns. According to the results of molecular diagnostics, 33 deletions were not detected in 33 patients (36.3%) of 32 families (39.5%), and major gene deletions were detected in 58 patients (63.7%) of 49 families (60.5%) dystrophin of various lengths - from one to nine exons: in 65.3% of families, extended deletions were verified, deletions of one exon were found in 34.7% of families. The main deletion spectrum was located in the distal part of the dystrophin gene - the 3'-end (deletions of 40-60 exons), which amounted to 81.6% (40 families, 47 patients). [ABSTRACT FROM AUTHOR]

We report on the molecular detection of two microduplications involving chromosomes Xp21.1–Xp21.2 and 17p12 in a 35-year-old female with clinical phenotype of Charcot–Marie–Tooth disease type 1A (CMT1A) documented by chromosomal microarray analysis. The 17p12 microduplication was approximately 1.32 Mb in size and contained eleven genes including the peripheral myelin protein 22 (PMP22), while the Xp21.1–Xp21.2 microduplication was estimated to be 626 Kb in size and contained part of the dystrophin (DMD) gene. Constitutional interstitial microduplication of 17p12 segment encompassing the PMP22 gene has been reported in individuals with Charcot–Marie–Tooth disease type 1A. Defects in the DMD gene (deletion, duplication, or mutation) are associated with Duchenne and Becker muscular dystrophies (DMD and BMD). Combined microduplications of Xp21/DMD with 17p12/PMP22 are extremely rare with only one published report of a male patient with changes in both the DMD and PMP22 genes.

Objective: In India, various groups have studied different regions to find out deletion pattern of dystrophin gene. We have investigated its deletion pattern among Duchenne/Becker muscular dystrophy (D/BMD) patients across Gujarat. Moreover, in this study we also correlate the same with reading frame rule. However, we too consider various clinicopathological features to establish as adjunct indices when deletion detection fails. Materials and Methods: In this pilot study, a total of 88 D/BMD patients consulting at our centers in Gujarat, India were included. All patients were reviewed on basis of their clinical characteristics, tested by three primer sets of 10-plex, 9-plex, and 7-plex polymerase chain reaction (PCR) for genetic analysis; whereas, biochemical indices were measured using automated biochemical analyzers. Results: The diagnosis of D/BMD was confirmed by multiplex-PCR (M-PCR) in D/BMD patients. A number of 65 (73.86%) out of 88 patients showed deletion in dystrophin gene. The exon 50 (58.46%) was the most frequent deletion found in our study. The mean age of onset of DMD and BMD was 4.09 ΁ 0.15 and 7.14 ΁ 0.55 years, respectively. In patients, mean creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and myoglobin levels were elevated significantly (P < 0.05) in comparison to controls. Addition to CPK, LDH and myoglobin are good adjunct when deletion detection failed. These data are further in accordance with world literature when correlated with frame rule. Conclusion: The analysis has been carried out for the first time for a total of 88 D/BMD patients particularly from Gujarat, India. More research is essential to elucidate specific mutation pattern in association with management and therapies of proband.

The development of clinical trials for Duchenne muscular dystrophy (DMD) in China faces many challenges due to limited information about epidemiological data, natural history and clinical management. To provide these detailed data, we developed a comprehensive database based on registered DMD patients from South China and analysed their clinical and mutational characteristics. The database included DMD registrants confirmed by clinical presentation, family history, genetic detection, prognostic outcome, and/or muscle biopsy. Clinical data were collected by a registry form. Mutations of dystrophin were detected by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Currently, 132 DMD patients from 128 families in South China have been registered, and 91.7% of them were below 10 years old. In mutational detection, large deletions were the most frequent type (57.8%), followed by small deletion/insertion mutations (14.1%), nonsense mutations (13.3%), large duplications (10.9%), and splice site mutations (3.1%). Clinical analysis revealed that most patients reported initial symptoms between 1 and 3 years of age, but the diagnostic age was more frequently between 6 and 8 years. 81.4% of patients were ambulatory. Baseline cardiac assessments at diagnosis were conducted in 39.4% and 29.5% of patients by echocardiograms and electrocardiograms, respectively. Only 22.7% of registrants performed baseline respiratory assessments. A small numbers of patients (20.5%) were treated with glucocorticoids. 13.3% of patients were eligible for stop codon read-through therapy, and 48.4% of patients would potentially benefit from exon skipping. The top five exon skips applicable to the largest group of registrants were skipping of exons 51 (14.8% of total mutations), 53 (12.5%), 45 (7.0%), 55 (4.7%), and 44 (3.9%). In conclusion, our database provided information on the natural history, diagnosis and management status of DMD in South China, as well as potential molecular therapies suitable for these patients. This comprehensive database will promote future experimental therapies in China. [ABSTRACT FROM AUTHOR]

In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation-a single exon 48 deletion of the dystrophin gene-who were affected with a very mild or subclinical form of BMD. They were usually detected thanks to accidental findings of elevated serum creatine phosphokinase (sCPK). A thorough clinical analysis of the carriers, both children (12) and adults (5), revealed in some of them muscle hypotonia (10/17) and/or very mild muscle weakness (9/17), as well as decreased tendon reflexes (6/17). Adults, apart from very mild muscle weakness and calf hypertrophy in some, had no significant abnormalities on neurological assessments and had good exercise tolerance. Parents of the children carriers of the exon 48 deletion are usually unaware of their children being affected, and possibly at risk of developing life-threatening cardiomyopathy. The same concerns the adult male carriers. Therefore, the authors postulate undertaking preventive measures such as cascade screening of the relatives of the probands. Newborn screening programmes of Duchenne muscular dystrophy (DMD)/BMD based on sCPK marked increase may be considered. [ABSTRACT FROM AUTHOR]