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Background: Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease due to mutations in the DMD gene, leading to a deficient and less functional dystrophin mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments., Materials and Methods: Retrospective data were collected from 943 patients diagnosed with BMD based on a combination of clinical, biochemical and genetic criteria followed by 17 Italian neuromuscular centers. Patients' demographics, main signs and symptoms at BMD onset, neuropsychiatric comorbidities, age at loss of ambulation (LoA), cardiac left ventricular ejection fraction (LVEF), pulmonary forced vital capacity (FVC), and DMD mutations were collected. Disease milestones were analysed in specific DMD mutational groups., Results: the median age at the last assessment was 26.0 (16.6-41.9) years, with a median age at diagnosis of 7.5 (4.0-14.0) years. In 55% of patients, the diagnosis was prompted by the incidental finding of hyperCKemia. At the last assessment, 13.5% of patients had lost the ability to walk at a median age estimated by Kaplan-Meier analysis of 69 years. Thirty percent of patients exhibited left ventricular impairment and 2.7% respiratory involvement. Ten percent of patients carried out-of-frame mutations, 4% nonsense mutations, and 86% in-frame deletions/duplications. The subset of in-frame deletions was further classified based on the specific mutations. Patients carrying del45-49 compared to del45-47 were associated with an earlier LoA (P=1×10-4), where patients with del45-55 (P=.005), del48 (P=.02), and del48-49 (P=.02) correlated with a later LoA compared to del45-47. del45-55 (P=.002) and del48 (P=.003) were significantly associated with decreased odds of developing a pathological LVEF% compared to del45-47., Conclusion: Our results contribute to the better understanding of the natural history of BMD and capture precious data in the era of the emerging therapies. The knowledge of the specific DMD mutation may help to define a prognosis in a subset of BMD patients and will serve as a model for the design of future therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The complete genome sequences with their annotations are a considerable resource in biology, particularly in understanding the global structure of the genetic material at the molecular level. The reason why some eukaryotic genomes contain large quantities of apparently unnecessary DNA, namely pseudogenes, while others seem to invest in more efficient thinning processes or are equipped with protection systems against parasitic elements still remains a mystery. Several genome-wide surveys have been undertaken to identify pseudogenes in the completely sequenced genome, bringing to light some differences both in their amount and distribution. Since pseudogenes are important resources in evolutionary and comparative genomics - as 'molecular fossils' - in this paper, a survey on the origins, features, abundance and localisation of the different pseudogenes is reported. As an example of genes producing processed pseudogenes, some experimental data obtained in the authors' laboratories from the study of a nuclear gene coding for the mitochondrial transcription factor A (mtTFA), a key regulator of mitochondrial biogenesis, are also reported.

We have determined the nucleotide sequences of thirteen rat mt tRNA genes. The features of the primary and secondary structures of these tRNAs show that those for Gln, Ser, and f-Met resemble, while those for Lys, Cys, and Trp depart strikingly from the universal type. The remainder are slightly abnormal. Among many mammalian mt DNA sequences, those of mt tRNA genes are highly conserved, thus suggesting for those genes an additional, perhaps regulatory, function. A simple evolutionary relationship between the tRNAs of animal mitochondria and those of eukaryotic cytoplasm, of lower eukaryotic mitochondria or of prokaryotes, is not evident owing to the extreme divergence of the tRNA sequences in the two groups. However, a slightly higher homology does exist between a few animal mt tRNAs and those from prokaryotes or from lower eukaryotic mitochondria.

We have sequenced the Eco R(1) fragment D from rat mitochondrial DNA. It contains one third of the tRNA (Val) gene (the remaining part has been sequenced from the 3' end of the Eco R(1) fragment A) the complete gene for the large mt 16S rRNA, the tRNA (Leu) gene and the 5' end of an unidentified reading frame. The mt gene for the large rRNA from rat has been aligned with the homologous genes from mouse and human using graphic computer programs. Hypervariable regions at the center of the molecule and highly conserved regions toward the 3' end have been detected. The mt gene for tRNA Leu is of the conventional type and its primary structure is highly conserved among mammals. The mt gene for tRNA(Val) shows characteristics similar to those of other mt tRNA genes but the degree of homology is lower. Comparative studies confirm that AGA and AGG are read as stop codons in mammalian mitochondria.

Theoretical analysis and experimental approaches by gel electrophoresis in retarding conditions allowed us to identify the presence of an intrinsic bending in the D-loop containing region of the rat mitochondrial genome. The curvature was located in the right domain of the sequence analyzed, between the origin of replication of the heavy strand and its promoter. The preliminary evidence of a specific recognition of the bent DNA with mitochondrial matrix proteins suggests a probable role of this DNA conformation in the duplication and/or expression of the mammalian mitochondrial genome.