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The emergence of therapies acting on specific molecular targets for Duchenne and Becker muscular dystrophies (DBMD) led to expanded access of diagnostic DMD analysis. However, it is unclear how much of these advances have also improved healthcare and access to genetic testing for women at-risk of being carriers. This study evaluates the process of genetic counseling and empowerment of genetic information by women from DBMD families. We carried out a cross-sectional study between February and June 2022 in Brazil. The online survey with items regarding sociodemographic data; family history; access to health services; reproductive decisions; and the Genomic Outcome Scale was answered by 123 women recruited from a rare diseases reference service and a nationwide patient advocacy group. Genetic counseling was reported by 77/123 (62.6%) of women and 53.7% reported having performed genetic analysis of DMD. Although the majority knew about the risks for carriers of developing heart disease and muscle weakness, only 35% of potential carriers have had cardiac studies performed at least once in their lives. Country region, type of kinship, number of affected males in the family, age, notion of genetic risk, education level, and participation in advocacy groups were the main factors associated with adequate healthcare access to women and empowerment of genetic information. Education to health professionals and policies to expand access to carrier genetic testing, whether public policies or regulation of pharmaceutical companies' diagnostic programs, is paramount to improve the care of families with DBMD in Brazil.

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BACKGROUND: Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common human dystrophinopathies with recessive X-linked inheritance. Dystrophin gene deletions and duplications are the most common mutations, followed by point mutations. The aim of this study is to characterize the mutational profile of the dystrophin gene in Colombian patients with DMD/BMD. MATERIAL AND METHODS: Mutational profiling was determined in 69 affected patients using Sanger sequencing, next-generation sequencing (NGS) and/or multiplex ligation dependent-probes amplification (MLPA). Genetic variants were classified according to molecular consequence and new variants were determined through database and literature analysis. RESULTS: Mutational profile in affected patients revealed that large deletions/duplications analyzed by MLPA accounted for 72.5% of all genetic variations. By using Sanger sequencing or NGS, we identified point mutations in 15.9% and small deletions in 11.6% of the patients. New mutations were found, most of them were point mutations or small deletions (10.1%). CONCLUSION: Our results described the genetic profile of the dystrophin gene in Colombian patients with DMD and contribute to efforts to identify molecular variants in Latin American populations. For our population, 18.8% of cases could be treated with FDA or MDA approved molecular therapies based on specific mutations. These data contribute to the establishment of appropriate genetic counseling and potential treatment.

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BACKGROUND: We report the molecular analysis of the DMD gene in a group of Peruvian patients with Duchenne/Becker dystrophinopathy. This is the first study to thoroughly characterize mutations in this population. METHODS: We used the combination of multiplex ligation-dependent probe amplification (MLPA) and sequencing analysis of the DMD gene. We recruited Peruvian patients in 2 years from reference national hospitals. We performed DNA tests in 152 patients, checking first exon deletion/duplication by MLPA, and subsequently, if negative, samples were sequenced to detect point mutations. RESULTS: The average age for diagnosis was 9.8 years, suggesting a delay for timely diagnosis and care. We found causal DMD mutations in 125 patients: 72 (57.6%) exon deletions/duplications (41.6% deletions, 16.0% duplications), and 53 (42.4%) point mutations (27.2% nonsense, 9.6% small indels, and 5.6% splice site). CONCLUSION: Due to our genetic background, we expected a higher number of novel and recurrent causal mutations in our sample. Results showed 16% of novel mutations, similar to other well-studied populations.

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Dystrophinopathies are a group of X-linked neuromuscular disorders that result from pathogenic variants in the DMD gene. Their pathophysiological substrate is the defective expression of dystrophin in many tissues. While patients from the same pedigree usually present similar dystrophin expression and clinical course, the extent of cardiac and skeletal muscle involvement may not correlate in the same individual. We identified a new splice site variant c.2803+5G>C (NM_004006) ClinVar VCV000803902, located in intron 22 of DMD in a Brazilian family that present a broad phenotypic and histological heterogeneity. One of the subjects had a typical Duchenne muscular dystrophy (DMD) phenotype, whereas the others had Becker muscular dystrophy (BMD). Cardiac involvement was remarkable in some of the BMD patients, but not in the DMD patient. Western blot analysis of skeletal muscle revealed much lower levels of calsequestrin in the most severely affected patient compared to his brother, whose phenotype is BMD, highlighting the potential role of proteins involved in skeletal muscle calcium homeostasis in differential degrees of dystrophinopathies.

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Introducción: Las distrofias musculares son las enfermedades degenerativas más comunes dentro de las enfermedades neuromusculares, cursan con debilidad muscular que progresa hasta la pérdida de la deambulación y en la segunda década de vida surgen complicaciones cardíacas, respiratorias y ortopédicas. Objetivo: Analizar el estado actual de los tratamientos génico y farmacológico en las distrofias musculares de Duchenne y Becker Métodos: Se realizó una búsqueda en los meses de enero, febrero y marzo de 2018 en las bases de datos Medline, Cinhal, Web Of Science y Scopus. Se obtuvieron 232 resultados y después de aplicar los criterios de inclusión y exclusión, se consiguieron para analizar 15 artículos válidos para la revisión. Resultados: Los artículos analizados investigan mayoritariamente el efecto de las terapias mencionadas a nivel de funcionalidad y de síntesis de la proteína distrofina durante períodos largos, en los que participan muestras de tamaño y edades variadas tanto como distrofia muscular de Duchenne y como distrofia muscular de Becker. Conclusiones: Existen más artículos enfocados en la distrofia muscular de Duchenne que en la distrofia muscular de Becker. Esto puede ser debido a que la primera es la más grave y de peor pronóstico. Sigue siendo necesario realizar más estudios para avanzar sobre el estado actual de estos tratamientos(AU)

Introduction: Muscular dystrophies are one of the most common degenerative pathologies within neuromuscular diseases. They present muscular weakness that develops until loss of wandering and in the second decade of life can appear cardiac, respiratory and orthopaedic complications. Objective: To know the current state of genetic and pharmacology treatments in the Duchenne and Becker muscular dystrophies. Methods: A search was made from January to March 2018 at Medline, Cinhal, Web Of Science and Scopus databases. 232 results were obtained, and applying the inclusion and exclusion criteria, 15 acceptable articles for reviewing were found. Results: Analyzed articles mostly investigate the effect of the mentioned therapies in the levels of functionality and dystrophin protein synthesis during long periods, in which samples of different sizes and ages are used. Conclusions: There are more articles focused on Duchenne Muscular Dystrophy than Becker Muscular Dystrophy. That can be due to the fact that the first is the most severe and with the worst prognosis. It is still necessary to carry out more scientific studies to move forward from the current stage of these treatments(AU)

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Different types of mutations in the DMD gene underlie Duchenne muscular dystrophies (DMD) and Becker muscular dystrophies (BMD). Large deletions and duplications are the most frequent causative genetic alterations worldwide, but little is known about DMD/BMD genetic profile in Brazil. Hence, we recruited patients with DMD and BMD from 8 neuromuscular reference centers along the country, and performed a comprehensive molecular investigation that included Multiplex Ligation-dependent Probe Amplification and Next generation sequencing (NGS) analyses. We evaluated 199 patients from 177 unrelated families: 166 with DMD, 32 with BMD and 1 1.5 years old asymptomatic patient with persistent hiperCKemia. Overall, large deletions (58.2%) followed by nonsense mutations (12.4%) and large duplications (11.3%) were the most frequent variants in Brazilian families. Large deletions were less frequent in BMD than in DMD (44.8% vs 60.8%). We identified 19 new DMD variants. Nonsense mutations were significantly more frequent in patients from northeastern region than from southern/southeastern regions of Brazil (27.7% vs 8.5%, P < .05). Genetic profile of Brazilian patients with DMD/BMD is similar to previously reported cohorts, but it is not uniform across the country. This information is important to plan rational clinical care for patients in face of the new coming mutation-specific therapies.

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BACKGROUND: Duchenne and Becker Muscular Dystrophy (DMD and BMD, respectively), are common forms of inherited muscle disease. Information regarding the epidemiology of these conditions, including genotype, is still sparse. OBJECTIVE: To establish the prevalence and genetic profile of DMD and BMD in Puerto Rico. METHODS: We collected data from medical records in all Muscular Dystrophy Association (MDA) clinics in Puerto Rico in order to estimate the prevalence of DMD and BMD and to describe the genotypic profile of these patients. Patients selected for data analysis matched "definite", "probable" and "possible" case definitions as established by MD STARnet. RESULTS: A total of 141 patients matched the inclusion criteria, with 64.5% and 35.5% being categorized into DMD and BMD, respectively. DMD and BMD prevalence in Puerto Rico was estimated at 5.18 and 2.84 per 100,000 males, respectively. Deletion was the most common form of mutation (66.7%) in the dystrophin gene, with exons in segment 45 to 47 being the most frequently affected. CONCLUSIONS: This is the first report of the prevalence and genetic profile characteristics of DMD and BMD in Puerto Rico. Prevalence of DMD was similar to that reported worldwide, while prevalence of BMD was higher. Genetic profile was consistent with that reported in the literature.

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OBJECTIVE: To provide weight-for-age, height-for-age, and body mass index-for-age growth reference standards for ambulatory, steroid-naïve males, ages 2-12 years, with Duchenne muscular dystrophy (DMD) and to compare these growth curves to the 2000 Centers for Disease Control and Prevention growth charts for boys, which serve as references of physical size and growth for the general male pediatric population in the US. STUDY DESIGN: Through a multi-state population-based surveillance of individuals with muscular dystrophy, a total of 1877 weight and 1544 height measurements ascertained during 1985-2010 from 513 males with DMD were obtained retrospectively from medical record review. Cases were classified as DMD if loss of ambulation occurred before the 12th birthday or, if younger than 12 years and still ambulating, the earliest symptoms of dystrophinopathy occurred before the 6th birthday. Each growth chart was constructed using 5 percentiles: 10th, 25th, 50th, 75th, and 90th. Smoothing procedures were applied in 2 stages to the irregular plots of the empirical percentile values. RESULTS: A set of growth curves, derived from a large cohort of male youth with DMD, are presented. These curves demonstrate that DMD males are shorter and tend to the extremes of weight and body mass index compared with the general male pediatric population in the US. CONCLUSION: Charts representing the pattern of growth in ambulatory, steroid-naïve males with DMD can facilitate monitoring of growth and early detection of unusual growth patterns. Use of these growth standards also will assist in monitoring responses to corticosteroid treatment.

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Objetivo: O objetivo foi avaliar portadores de distrofia muscular de Duchenne (DMD) e Becker (DMB) por meio de escalas e análise postural. Metodologia: Foram avaliados 13 pacientes, idade 16,75 (± 6,9) sendo 9 DMD, 4 DMB, 7 cadeirantes, 6 não cadeirantes, nas escalas: Índice de Barthel e EK (Egen klassifikation). A avaliação postural sentada foi feita no software SAPO. Resultados: Os dados revelam que: aumento da idade (p<0.01), dependência de cadeira de rodas (p<0.01) e uso de ventilador (p<0.01) indicaram menor independência. Na avaliação postural tanto dos não cadeirantes quanto dos cadeirantes, verificou-se que aumentam os agrupamentos nos cadeirantes, remetendo às limitações impostas pela postura. Conclusão: Esses achados mostram que pacientes com DMD e DMB têm sua funcionalidade e atividades de vida diária debilitadas com o avanço da idade, dependência de cadeira de rodas e uso de ventilador. Assim, associação de escalas com avaliações convencionais e análise postural são ferramentas essenciais para a investigação.

Objective: The objective was to evaluate patients with Duchenne muscular dystrophy (DMD) and Becker (BMD) in scales and postural analysis. Methods: We evaluated 13 patients, age 16.75 (± 6.9) and 9 DMD, BMD 4, 7 wheelchair, wheelchair not 6, on the scales: Barthel Index and EK (Egen Klassifikation). The evaluation was performed in sitting posture software SAPO. Results: Data show that: increasing age (p <0.01), dependence on a wheelchair (p <0.01) and use of ventilator (p <0.01) showed less independence. Postural assessment of both the wheelchair and not the wheelchair, it was found that increase in the wheelchair groups, referring to the restrictions imposed by posture. Conclusion: These findings show that patients with DMD and BMD have its functionality and activities of daily living impaired with advancing age, dependence on a wheelchair and ventilator use. Thus, association of scales with conventional assessments and postural analysis are essential tools for research.

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Deletions/duplications in the Duchenne muscular dystrophy (DMD) gene account for 60 to 70% of all alterations. A new technique, multiplex ligation-dependent probe amplification (MLPA), has been described that allows the detection of large genetic rearrangements by simultaneous amplification of up to 45 target sequences. The present article is based on the diagnosis of the first Argentine affected families by the application of MLPA. DNA samples from patients with and without a previous diagnosis were included. MLPA assays were performed according to manufacturer recommendations. Polymerase chain reaction and direct sequencing were performed when a single-exon deletion was detected. Results were analyzed using the Gene Marker v1.6 and Sequencing Analysis v5.2 software. In the samples with a previous diagnosis (as identified by short tandem repeat-polymerase chain reaction analysis), MLPA confirmed in some samples the same deletion and detected in others a larger deleted fragment. This enabled the prediction of the expected male phenotype. One deletion and one duplication were detected in patients without previous diagnosis. In this study, we investigated the applicability of MLPA in our country. Our results showed a 100% confirmation of the deleted fragments detected by short tandem repeat segregation analysis. Moreover, in some cases, the MLPA assay was able to refine the breakpoints involved. In addition, MLPA identified deletions/duplications in samples without previous diagnosis. In comparison to the available diagnosis strategies in Argentina, MLPA is less time-consuming, and spans the complete coding region of DMD. The application of MLPA will improve the genetic diagnosis of DMD/Becker muscular dystrophy in our country.

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