Diagnosis Of Becker Muscular Dystrophy Research Articles

Clinical Response of Levodopa in CTNNB1-Related Dystonia

Abstractβ-catenin, which is encoded by the CTNNB1 gene, is essential for the development and functioning of the brain. There are a few documented cases of dystonia related to CTNNB1. Here, we report the case of an 11-year-old Spanish boy referred for movement disorders and gait disturbance. He had motor developmental delay and achieved unassisted walking at 3 years, with a tiptoe gait and valgus foot posture requiring ankle-foot orthoses. Blood tests showed elevated creatine kinase levels (1684 U/L, normal range 62–235). Molecular analysis revealed a deletion in exons 3-9 of the DMD gene, leading to the diagnosis of Becker muscular dystrophy. By age 8, he presents frequent falls due to a dystonic posture of the feet and abnormal movements in the upper and lower limbs. Whole-exome sequencing revealed a novel heterozygous, de novo pathogenic frameshift variant in the CTNNB1 gene (NM_001098209.1):p.Thr297fs/ c.889dupA. Treatment with levodopa/carbidopa (5.3 mg/kg/day) led to a partial clinical improvement, including a decrease in dystonia, measured by the Burke-Fahn-Marsden Dystonia Rating Scale, and choreic movements in all four limbs. We suggest that levodopa contributes to motor improvement in patients with CTNNB1-related dystonia, supporting its inclusion in the differential diagnosis of childhood dopa-responsive dystonia.

Clinical and genetic interpretation of uncertain DMD missense variants: evidence from mRNA and protein studies

BackgroundPathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies.MethodsNine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them.ResultsThree of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn’t reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively.ConclusionOur study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.

Electrocardiographic Changes in Jordanian Patients With Becker Muscular Dystrophy.

Background and aim Becker muscular dystrophy (BMD) is an X-linked disease caused by an in-frame mutation in the dystrophin gene, which is considered an allelic disorder to the most severe form of dystrophinopahies, Duchenne muscular dystrophy, which leads to skeletal and cardiac muscle involvement and results in dilated cardiomyopathy (DCM). The aim of this study is to present our ECG data and the significance of this data in the early detection of DCM in these patients. Methods This is a retrospective study. All patients known to the clinical Genetic Clinic and Queen Alia Heart Center in Jordan with a diagnosis of Becker muscular dystrophy from the year 2011-2022 are offered cardiac evaluation according to the guidelines, which included clinical assessment, electrocardiograph, and 2-D echocardiograph(echo)at the time of diagnosis and every five years thereafter once the initial assessment was normal. All the records were retrieved and analyzed. Results Fifty-three patients of all ages with genetically confirmed BMD were identified. Twelve had no record as they didn't attend any cardiac evaluation. Forty-one were under regular clinical follow-up. Two were excluded as they died, and another four had no recorded data in our center. Ultimately, 35 patients were included and studied. The mean age was 30.5 years ± 22.1, ranging from two to seventy-seven years of age. Twenty-seven (77%) had abnormal ECG. High voltage R wave in V2 and V1 was the most common finding, followed by repolarisation abnormalities and Q wave (43%, 17%, 13%, and 11% respectively). Incomplete right bundle branch block in 4% as well as R/S ratio >1.2. U wave abnormalities in 3% and sinus tachycardia were found in only one patient. Conclusion Cardiac surveillance for patients with Becker muscular dystrophy is mandatory after the age of 16. Q wave and repolarisation changes should be taken seriously as early signs of dilated cardiomyopathy,even if the echo is normal.

Exonization of a deep intronic long interspersed nuclear element in Becker muscular dystrophy.

The precise identification of pathogenic DMD variants is sometimes rather difficult, mainly due to complex structural variants (SVs) and deep intronic splice-altering variants. We performed genomic long-read whole DMD gene sequencing in a boy with asymptomatic hyper-creatine kinase-emia who remained genetically undiagnosed after standard genetic testing, dystrophin protein and DMD mRNA studies, and genomic short-read whole DMD gene sequencing. We successfully identified a novel pathogenic SV in DMD intron 1 via long-read sequencing. The deep intronic SV consists of a long interspersed nuclear element-1 (LINE-1) insertion/non-tandem duplication rearrangement causing partial exonization of the LINE-1, establishing a genetic diagnosis of Becker muscular dystrophy. Our study expands the genetic spectrum of dystrophinopathies and highlights the significant role of disease-causing LINE-1 insertions in monogenic diseases.

Detection of the mutation may guide treatment of heart and muscle in Duchenne muscular dystrophy.

We read with great interest the article, by Kono et al, about a 32-year-old male with Duchenne muscular dystrophy (DMD), who was admitted for dilated cardiomyopathy manifesting as heart failure, left bundle branch block, Mobitz-II block, bradycardia, and arterial hypotension. He profited from implantation of a cardiac resynchroniza-tion therapy-D system with a defibrillator and beta-blocker treatment. 1 We have the following comments and concerns. Diagnosing DMD only by muscle biopsy is insufficient. The diagnosis needs to be confirmed by genetic studies. 2 Was the patient investigated for deletions, duplications , or point mutations in the DMD gene? Which were the results of the Western blot for dystrophin? Was there complete absence of dystrophin or were there indications for a truncated protein, compatible with the diagnosis of Becker muscular dystrophy (BMD)? Since the patient was quite old for DMD, it has to be convincingly shown that BMD was definitively excluded. Diagnosing DMD on a molecular genetic level is important as genetic therapy in form of exon skipping is available for a certain type of mutations. 3 It has been shown that patients with DMD profit from the administration of ste-roids, usually deflazacort. 4 There are indications that steroids not only improve the performance of the skeletal muscle but also improve cardiac functions. 5 Furthermore, steroids reduce the myocardial fibrosis burden in these patients as has been shown by cardiac magnetic resonance imaging (MRI). 6 Did the presented patient receive steroids in addition to heart failure therapy? Did he profit from steroids with regard to cardiac and muscle function? Which side effects did he develop from steroids? Dilated cardiomyopathy in DMD is characterized by replacement of the myocar-dium with connective tissue. 6 Myocardial fibrosis in DMD can be best documented by application of cardiac MRI and administration of gadolinium to assess the amount of late gadolinium enhancement (LGE). 6 Did the patient undergo cardiac MRI and was gadolinium administered to assess the amount and location of myocardial fibrosis? Assessment of LGE in DMD is important since the amount of LGE strongly correlates with left ventricular systolic dysfunction. 6 Approximately two-thirds of the DMD patients inherit the mutation from their mothers. DMD carriers may manifest clinically or biochemically. Was the mother of the described patient investigated for her carrier status? Did she manifest clinically or were there other indications for being a DMD carrier? Did she undergo electrocardiography

Diagnosis of becker muscular dystrophy: Results of Re-analysis of DNA samples.

The phenotype of Becker muscular dystrophy (BMD) is highly variable, and the disease may be underdiagnosed. We searched for new mutations in the DMD gene in a cohort of previously undiagnosed patients who had been referred in the period 1985-1995. All requests for DNA analysis of the DMD gene in probands with suspected BMD were re-evaluated. If the phenotype was compatible with BMD, and no deletions or duplications were detected, DNA samples were screened for small mutations. In 79 of 185 referrals, no mutation was found. Analysis could be performed on 31 DNA samples. Seven different mutations, including 3 novel ones, were found. Long-term clinical follow-up is described. Refining DNA analysis in previously undiagnosed cases can identify mutations in the DMD gene and provide genetic diagnosis of BMD. A delayed diagnosis can still be valuable for the proband or the relatives of BMD patients.

Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient

We report a dystrophinopathy patient with an in-frame deletion of DMD exons 45–47, and therefore a genetic diagnosis of Becker muscular dystrophy, who presented with a more severe than expected phenotype. Analysis of the patient DMD mRNA revealed an 82 bp pseudoexon, derived from intron 44, that disrupts the reading frame and is expected to yield a nonfunctional dystrophin. Since the sequence of the pseudoexon and canonical splice sites does not differ from the reference sequence, we concluded that the genomic rearrangement promoted recognition of the pseudoexon, causing a severe dystrophic phenotype. We characterized the deletion breakpoints and identified motifs that might influence selection of the pseudoexon. We concluded that the donor splice site was strengthened by juxtaposition of intron 47, and loss of intron 44 silencer elements, normally located downstream of the pseudoexon donor splice site, further enhanced pseudoexon selection and inclusion in the DMD transcript in this patient.

G.P.1: Refinement of diagnosis of Becker muscular dystrophy: Results of re-analysis of DNA samples

The phenotype of Becker muscular dystrophy (BMD) is highly variable, and thus the disorder might be underdiagnosed. In this study we have reviewed the undiagnosed cases among patients referred for suspected BMD in the period 1985–1995. At that time DNA analysis of the DMD gene was the only routinely available diagnostic test for patients suspected of having muscular dystrophy. Over the last decade sequencing techniques have been developed for the detection of small mutations in the DMD gene. Our aim was to investigate whether BMD had been genetically underdiagnosed in the early decade of DNA analysis and, if so, whether we could improve the diagnostic yield by applying new techniques. Previously, in 79 of 185 referrals for BMD testing no deletions or duplications had been found. The original requisition forms for DNA analysis were re-evaluated; Forty-six cases were excluded because clinical data were lacking or not suggestive for BMD or the patients were known to be deceased. In 33 cases the clinical information was compatible with BMD and those were considered potentially relevant for re-analysis of the DMD gene. Sequencing could be performed on 31 stored DNA samples. Six different mutations, including four novel ones, were found. Long term clinical follow-up in these adult males revealed that one patient was asymptomatic, one had mild symptoms and four had lost ambulation due to progressive limb girdle weakness. Conclusion: We conclude that extending DNA analysis by sequencing the DMD gene can be helpful in identifying BMD in male patients in whom previously no deletions or duplications were found. A delayed diagnosis can still be valuable for the proband or the relatives of the BMD patients.

G.P.5: Clinical profile of a 6-year old boy with Becker Muscular Dystrophy and asymptomatic rhabdomyolysis: A case report

<i>Background:</i> There have been several reports in the literature of exercise-related muscle cramps and myoglobinuria, or asymptomatic myoglobinuria leading to a diagnosis of Becker Muscular Dystrophy (BMD). <i>Objective:</i> To present the complete clinical profile of a child with BMD with asymptomatic rhabdomyolysis, and to contribute to natural history data. <i>Case report:</i> MG is a 6 year old male referred with a dystrophinopathy. He had exercise-induced cramps in his legs and a tendency to toe-walk at age 4. CPK was 8100. He had an Xp21.1 gain-of-function mutation on chromosomal microarray, and an in-frame duplication of exons 17–25 of the dystrophin gene. His initial exam was normal with the exception of mild hypotonia and pronated feet. Muscle MRI of his pelvic and thigh muscles showed minimal fatty changes. Muscle biopsy showed mild dystrophic changes (some increased centrally located nuclei, perimysial fibrosis, minimal necrotic fibers, and minimal fibrofatty changes) with significantly decreased staining for dys3 antibody. Western blot analysis indicated between 20% and 100% of muscle dystrophin confirming BMD. At follow-up, he reported a single episode of dark urine the prior evening which spontaneously resolved, without cramps, pain, or fatigue. Examination was normal. Post-visit labs were notable for rhabdomyolysis (CPK 56 100, AST 930, ALT 675, myoglobin 555). Labs 1week later showed a persistently elevated myoglobin (537), baseline CPK (6182), AST (163), and ALT (332), and normal urinalysis. The patient remained asymptomatic, and was advised to continue aggressive hydration. <i>Conclusion:</i> Our case describes the complete clinical profile (including pathology, dystrophin status, and muscle MR) of a patient with BMD with an episode of asymptomatic rhabdomyolysis. This case highlights the need to appropriately screen children, to provide anticipatory guidance on monitoring and management of rhabdomyolysis to families, and provides natural history data on the disease.

D.P.21 Reliability and accuracy of skeletal muscle imaging in limb girdle muscular dystrophies

Objective: To evaluate the reliability and accuracy of skeletal muscle computed tomography to correctly identify different muscular dystrophies manifesting with limb girdle weakness. Four evaluators assessed scans from 118 patients with limb girdle muscular dystrophy caused by mutations in seven different genes and from 32 controls. The conditions studied were scans of genetically confirmed cases of Becker muscular dystrophy (BMD) [n=28], LGMD2C-F (Sarcoglycanopathies) [n=11], LGMD2I [n=4], LGMD1B [n=26], LGMD2A [n=24], Bethlem myopathy [n=14] and LGMD2L [n=11]. The control group [n=32] consisted of patients affected by muscular dystrophies manifesting with limb girdle weakness in which the aforementioned muscular dystrophies were excluded. The scans were compared with the characteristic patterns described in literature. The overall interobserver agreement was poor (κ=0,27), with markedly higher scores for Becker muscular dystrophy (κ=0,51) and Bethlem myopathy (κ=0,59). The sensitivity to detect selective patterns in relation to the genetic diagnosis was 40% if all limb girdle muscular dystrophies were taken together. The specificity was 58%, positive predictive value (PPV) 77% and 1-negative predictive value (1-NPV) 79%. Markedly better scores were observed for Becker muscular dystrophy (sensitivity 91%, PPV 66%, 1-NPV 3%) and Bethlem myopathy (sensitivity 90%, PPV 69%, 1-NPV 1%). Our findings suggest that muscle computed tomography might be an adjunct to the clinical diagnosis of Becker muscular dystrophy and Bethlem myopathy. However, pattern recognition was cumbersome in the other limb-girdle muscular dystrophies.

Childhood Pneumonectomies: Two Decades' Experience of a Referral Center

We aimed to review the pre- and postoperative characteristics of children undergoing pneumonectomy, with special emphasis on the management of surgical complications, in comparison with the current literature findings. A total of 20 patients who underwent pneumonectomy for various etiologies from 1988 to 2011 were investigated retrospectively with respect to the presenting findings, preoperative evaluation, surgical information, postoperative follow-up, and outcome. A total of 11 girls and 9 boys with a median age of 8 years (0.5-17 years) presented with symptoms of productive cough (n = 9), recurrent chest infections (n = 9), nonproductive cough (n = 1), respiratory distress (n = 1) with a median duration of 2 years (0.16 to 12 years). Medical histories revealed chest infection (n = 11), foreign body aspiration (n = 3), aspiration pneumonia (n = 2), tuberculosis (n = 2), caustic aspiration (n = 1), and congenital lung pathology (n = 1). Clinical evaluation provided diagnoses of bronchiectasis (n = 16), total atelectasis (n = 2), bronchopleural fistula (BPF) (n = 1), and cystic lung disease (n = 1). Pneumonectomy was performed on the right in 6 and left in 14 of the cases. Pericardial (n = 1) and esophageal (n = 1) laceration were the perioperative (11.1%), massive hemorrhage (n = 1) and chylothorax (n = 1) the postoperative (11.1%), and scoliosis (n = 1) and BPF (n = 1) the long-term (11.1%) complications. Pathological evaluation revealed bronchiectasis (n = 14), consisting of three cases with additional sign of foreign body, chronic inflammation (n = 4), atelectasis with fibrous pleural thickening (n = 1), and congenital pulmonary lymphangiectasia (n = 1). A total of 14 cases were free of symptoms and 5 had significant improvement in general condition during the follow-up, for a median duration of 2 years (1 to 10). The one with the diagnosis of Becker muscular dystrophy died 2 years after pneumonectomy because of respiratory failure. Correct selection of indications, careful preoperative preparation with eradication of infection, meticulous performance of surgical and anesthetic techniques, early detection and management of complications, and long-term follow-up including pulmonary rehabilitation are essential parameters to reduce morbidity and mortality rates in childhood pneumonectomy. Better compensatory lung growth and improvement in development after the operation will facilitate better health and improved life quality in children.

Coinheritance of Noonan syndrome and Becker muscular dystrophy

We describe for the first time a case of a 9-year old boy with co-existence of dystrophinopathy and Noonan syndrome (NS). Although the patient has a severe muscular clinical phenotype, consistent with Duchenne muscular dystrophy (DMD), the diagnosis of Becker muscular dystrophy (BMD) was proposed based on family history (brother with BMD) and confirmed by muscle immunohistochemistry, and molecular study shown an in-frame DMD gene mutation. The patient also fulfilled the clinical criteria of NS and he harbors a hotspot mutation on PTPN11 gene. This genetic combination may be an explanation for the variability of clinical expression in the family.

P.P.4 07 Phenotype and muscle biopsy findings in the first German patient with limb-girdle muscular dystrophy 2K – Important differential diagnosis of Becker muscular dystrophy

P.P.4 07 Phenotype and muscle biopsy findings in the first German patient with limb-girdle muscular dystrophy 2K – Important differential diagnosis of Becker muscular dystrophy

Absence of neuronal nitric oxide synthase (nNOS) as a pathological marker for the diagnosis of Becker muscular dystrophy with rod domain deletions.

Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is localized to the sarcolemma. In rare cases, however, this labelling is equivocal and similar to that observed in controls making diagnosis difficult. We report here that in such instances immunolabelling with antibodies to the neuronal form of nitric oxide synthase (nNOS) can be useful in suspecting a dystrophinopathy with a mutation in the 'hot-spot' rod domain and help to direct molecular analysis. nNOS localizes to the sarcolemma of mature muscle fibres via several components of the dystrophin-associated protein complex (DAPC) including dystrophin but sarcolemmal nNOS is lost when dystrophin levels are very low or absent because of deletions in critical regions of the rod domain. We report three cases who presented with only mild or no muscle weakness but had elevated serum creatine kinase activity and dystrophin immunolabelling indistinguishable from normal, making a pathological diagnosis difficult. All three cases had a complete absence of sarcolemmal nNOS and were subsequently found to have an in-frame deletion in the common rod domain exons (in these cases 48, 45-51, 47-53) compatible with a BMD. In addition, we observed that nNOS appears to be developmentally regulated with the antibody used and was often absent from the sarcolemma of immature fibres. These findings demonstrate the value of including antibodies to nNOS in routine immunohistochemical studies and that absence of nNOS can be a more sensitive marker than up-regulation of utrophin for diagnosis of BMD. Immaturity of fibres, however, needs to be taken into account, especially in neonates.

Duplication of dystrophin gene and dissimilar clinical phenotype in the same family

We report here three related patients with a duplication of exons 19–41 of the dystrophin gene, having dissimilar clinical phenotype and dystrophin immunohistochemistry. Two brothers aged six and three years had myalgia, proximal muscular weakness and hypertrophic calves, with 10- to 20-fold increase of serum creatine kinase. Muscle biopsy showed dystrophic changes and reduced, patchy binding of dystrophin. The clinical and laboratory findings were consistent with a diagnosis of Becker muscular dystrophy with early onset. Their 14-year-old cousin had only mild hyperCKemia. His muscle biopsy was normal with only mild reduction of dystrophin immunostaining. At follow-up, he is still without symptoms and signs at age 19. All three patients had the same gene duplication and an increased dystrophin size of 507 kDa. Expression of the dystrophin-associated glycoproteins adhalin, α-dystroglycan, and, β-dystroglycan were normal in the three patients. An intrafamilial variability in patients carrying a partial duplication of the dystrophin gene may be related to a quantitative difference in mRNA.

The diagnosis of Duchenne and Becker muscular dystrophies: two years' experience in a comprehensive carrier screening and prenatal diagnostic laboratory.

This article describes the diagnostic algorithm being used for the management of the 148 families affected by Duchenne or Becker muscular dystrophy who are known to the Molecular Neurogenetics Laboratory in the Department of Neuropathology, Royal Perth Hospital. In 60 families from whom DNA has been obtained, 41 mutations (39 deletions and two duplications) of the Duchenne muscular dystrophy gene (DMD) have been identified by means of complementary DNA (cDNA) probes. DNA-based screening has clarified the carrier status of 45 at-risk women, and 13 pregnancies have been monitored. In addition, cDNA screening of all relevant patients with autosomal recessive muscular dystrophy, spinal muscular atrophy or limb-girdle muscular dystrophy facilitated the correct diagnosis of Becker muscular dystrophy in three patients.

An unusual variant of Becker muscular dystrophy

We report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed vacuoles. DNA analysis revealed a deletion in the dystrophin gene, establishing a diagnosis of Becker muscular dystrophy. Both the absence of calf hypertrophy and the presence of rimmed vacuoles are unusual features in this disorder.

Enormous dystrophin in a patient with Becker muscular dystrophy

We describe a patient with a duplication of more than 400,000 bp of the dystrophin gene. The duplication is completely contained within the gene, and the duplicated exons are predicted to be "in frame" with the rest of the gene. Dystrophin protein is detected in the patient's muscle as a single species of approximately 600 kDa (normal, approximately 400 kDa), indicating that the resulting mutated gene codes for a translatable mRNA of over 100 exons (normal, approximately 70 exons). The patient's mother carries the duplicated gene as determined by both DNA and protein analysis. The described duplication of the dystrophin gene is by far the largest characterized to date. This observation is of significant biologic interest in that, despite the gross alteration of the gene and the encoded protein, the patient has a relatively mild clinical progression compatible with a diagnosis of Becker muscular dystrophy.

Differentiation of Becker muscular dystrophy from limb‐girdle muscular dystrophy and Kugelberg‐Welander disease using a cDNA probe

A 31-year-old man previously investigated for a neuromuscular disorder was diagnosed as having either limb-girdle dystrophy, spinal muscular atrophy, or Becker muscular dystrophy. Extensive clinical and special neurological investigations failed to clarify this differential diagnosis. However, recent DNA studies have shown a deletion of the dystrophin gene, thereby providing an unequivocal diagnosis of Becker muscular dystrophy. The application of molecular genetic techniques in the diagnosis of inherited neuromuscular disorders is discussed.

Dystrophin diagnosis: comparison of dystrophin abnormalities by immunofluorescence and immunoblot analyses.

Immunoblot characterization and immunofluorescence localization of dystrophin are presented for 76 human patients with various neuromuscular diseases. Normal dystrophin (shown by immunoblotting) was invariably visualized as a continuous, peripheral membrane immunostaining of myofibers. Biochemical abnormalities of dystrophin (either lower or higher molecular weight dystrophin) resulted in patchy, discontinuous immunostaining, suggesting that the abnormal dystrophin proteins are not capable of creating a complete membrane cytoskeleton network. There was a very strong correlation of clinical diagnoses with the type of dystrophin abnormality; all Duchenne muscular dystrophy patient muscle contained no detectable dystrophin, Becker muscular dystrophy patient muscle had clearly abnormal dystrophin, and unrelated diseases showed normal dystrophin. However, a single patient of five carrying the diagnosis of Fukuyama dystrophy showed no detectable dystrophin and thus appeared to be a Duchenne dystrophy patient by the biochemical assays. We know of no other case of a patient with a disease thought to be unrelated to Duchenne/Becker dystrophy yet demonstrating dystrophin deficiency. Based on the data presented, we conclude that immunofluorescence is the best technique for the detection of female carriers of Duchenne dystrophy, whereas immunoblotting appears superior for the prognostic diagnosis of Becker muscular dystrophy.