Rapid Molecular Diagnosis of Genetically Inherited Neuromuscular Disorders Using Next-Generation Sequencing Technologies

• Published in: Journal of clinical medicine Vol. 11; no. 10; p. 2750
• Main Authors: Barbosa-Gouveia, Sofia, Vázquez-Mosquera, Maria Eugenia, González-Vioque, Emiliano, Hermida-Ameijeiras, Álvaro, Sánchez-Pintos, Paula, de Castro, Maria José, León, Soraya Ramiro, Gil-Fournier, Belén, Domínguez-González, Cristina, Camacho Salas, Ana, Negrão, Luis, Fineza, Isabel, Laranjeira, Francisco, Couce, Maria Luz
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-05-2022; MDPI
• Subjects: Clinical medicine; Congenital diseases; Disease; Gene expression; Kinases; Laboratories; Muscular dystrophy; Myasthenia gravis; Patients; myopathy; next-generation sequencing; Phenomizer; neuromuscular disorders
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm11102750

Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). The global mean diagnostic rate was 36% (97/268 patients), with a diagnostic turnaround time of 4-6 weeks. Most diagnoses corresponded to muscular dystrophies/myopathies (68.37%) and peripheral nerve diseases (22.45%). The most common causative genes,
,
, and
, accounted for almost 30% of the diagnosed cases. Finally, we evaluated the utility of the differential diagnosis tool Phenomizer, which established a correlation between the phenotype and molecular findings in 21% of the diagnosed patients. In summary, comprehensive gene-panel analysis of all genes implicated in neuromuscular diseases facilitates a rapid diagnosis and provides a high diagnostic yield.