Ceroid lipofuscinosis type 5: novel pathogenic variants and unexpected phenotypic findings

Paiva, Anderson Rodrigues Brandão de; Pessoa, André Luiz Santos; Nóbrega, Paulo Ribeiro; Moreno, Cristiane Araújo Martins; Lynch, David S.; Taniguti, Lucas Mitsuo; Kitajima, João Paulo; Freua, Fernando; Della-Ripa, Bruno; Cunha, Paulina; Barcelos, Isabella Peixoto de; Macedo‐Souza, Lúcia Inês; Takeuchi, Carlos Augusto; Garcia, Antônio Milton Silva; Nardes, Flávia; Fontão, Ramiro; Antoniuk, Sérgio Antônio; Troncoso, Mónica; Spécola, Norma; Durand, Consuelo; Madeiro, Bianca de Aguiar Coelho Silva; Doriqui, Maria Juliana Rodovalho; Vergara, Diane; Houlden, Henry; Kok, Fernando

doi:10.1136/jnnp-2022-330135

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…However, we believe this is the largest single-center cohort in Latin America and the only one to include patients from the northeastern state of Ceará, where previous studies have documented significant inbreeding [29] and many novel ultra-rare disease-causing pathogenic variants have been described [30][31][32]. The implementation of strategies aimed at improving access to genetic investigations in isolated populations from underdeveloped countries may lead to the discovery of rare variants [54], expand the disease spectrum in previously described diseases [55,56] and help in differentiating disease-modifying variants from genetic variations caused by differences in ancestrality.…”

Section: Discussionmentioning

confidence: 94%

Higher Prevalence of Nonsense Pathogenic DMD Variants in a Single-Center Cohort from Brazil: A Genetic Profile Study That May Guide the Choice of Disease-Modifying Treatments

Braga,

Lima,

Mariano

et al. 2023

Brain Sciences

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Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs.

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