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. 2016 Jul 5;87(1):71-6.
doi: 10.1212/WNL.0000000000002800. Epub 2016 Jun 8.

The genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients

Marco Savarese  1 , Giuseppina Di Fruscio  1 , Annalaura Torella  1 , Chiara Fiorillo  1 , Francesca Magri  1 , Marina Fanin  1 , Lucia Ruggiero  1 , Giulia Ricci  1 , Guja Astrea  1 , Luigia Passamano  1 , Alessandra Ruggieri  1 , Dario Ronchi  1 , Giorgio Tasca  1 , Adele D'Amico  1 , Sandra Janssens  1 , Olimpia Farina  1 , Margherita Mutarelli  1 , Veer Singh Marwah  1 , Arcomaria Garofalo  1 , Teresa Giugliano  1 , Simone Sampaolo  1 , Francesca Del Vecchio Blanco  1 , Gaia Esposito  1 , Giulio Piluso  1 , Paola D'Ambrosio  1 , Roberta Petillo  1 , Olimpia Musumeci  1 , Carmelo Rodolico  1 , Sonia Messina  1 , Anni Evilä  1 , Peter Hackman  1 , Massimiliano Filosto  1 , Giuseppe Di Iorio  1 , Gabriele Siciliano  1 , Marina Mora  1 , Lorenzo Maggi  1 , Carlo Minetti  1 , Sabrina Sacconi  1 , Lucio Santoro  1 , Kathleen Claes  1 , Liliana Vercelli  1 , Tiziana Mongini  1 , Enzo Ricci  1 , Francesca Gualandi  1 , Rossella Tupler  1 , Jan De Bleecker  1 , Bjarne Udd  1 , Antonio Toscano  1 , Maurizio Moggio  1 , Elena Pegoraro  1 , Enrico Bertini  1 , Eugenio Mercuri  1 , Corrado Angelini  1 , Filippo Maria Santorelli  1 , Luisa Politano  1 , Claudio Bruno  1 , Giacomo Pietro Comi  1 , Vincenzo Nigro  1
Affiliations

The genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients

Marco Savarese et al. Neurology. .

Erratum in

Abstract

Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients.

Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy.

Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes.

Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions.

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Figures

Figure 1
Figure 1. Characteristics of recruited patients
(A) Percentage of male and female patients. (B) Geographical origin of patients. (C) Percentage of patients in 3 different categories (LGMD, CM, other conditions). (D) Mode of inheritance for the studied conditions. (E) Previous unsuccessful molecular tests performed in prescreened patients. CM = congenital myopathy; LGMD = limb-girdle muscular dystrophy.
Figure 2
Figure 2. Diagnostic rate and molecular results
(A) Definitive diagnosis was obtained in 43.2% of patients. In addition, 31.8% of patients showed variants that required further characterization. (B) Type of causative mutations identified in diagnosed patients: missense (64.9%), small indels (12.2%), splice-site variants (11.9%), and nonsense mutations (10.4%).
Figure 3
Figure 3. Distribution of the 504 patients tested according to clinical phenotype and molecular findings
A total of 125 patients (48.4%) with LGMD received a molecular diagnosis, 83 (32.2%) are still under consideration, and in 50 patients (19.4%), no clear causative variants were detected. A total of 64 patients (39%) with CM received a molecular diagnosis, 50 (30.5%) are still under investigation, and 50 (30.5%) showed no causative variations. A total of 29 patients (35.4%) with other clinical conditions received a molecular diagnosis, 27 (32.9%) are to be further investigated, and in 26 patients (31.7%), no causative variants were identified. CM = congenital myopathy; LGMD = limb-girdle muscular dystrophy.
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References

    1. Bonnemann CG, Wang CH, Quijano-Roy S, et al. . Diagnostic approach to the congenital muscular dystrophies. Neuromuscul Disord 2014;24:289–311. - PMC - PubMed
    1. Wicklund MP. The muscular dystrophies. Continuum 2013;19:1535–1570. - PMC - PubMed
    1. Iannaccone ST, Castro D. Congenital muscular dystrophies and congenital myopathies. Continuum 2013;19:1509–1534. - PMC - PubMed
    1. Reilly MM, Hanna MG. Genetic neuromuscular disease. J Neurol Neurosurg Psychiatry 2002;73(suppl 2):ii12–ii21. - PMC - PubMed
    1. Kaplan JC, Hamroun D. The 2015 version of the gene table of monogenic neuromuscular disorders (nuclear genome). Neuromuscul Disord 2014;24:1123–1153. - PubMed

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