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. 2024 May 15:15:1365729.
doi: 10.3389/fgene.2024.1365729. eCollection 2024.

Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients

Chung-Lin Lee  1   2   3   4   5 , Chih-Kuang Chuang  6   7 , Huei-Ching Chiu  1 , Ya-Hui Chang  1   3 , Yuan-Rong Tu  6 , Yun-Ting Lo  3 , Hsiang-Yu Lin  1   3   4   5   6   8 , Shuan-Pei Lin  1   3   4   6   9
Affiliations

Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients

Chung-Lin Lee et al. Front Genet. .

Abstract

Background: Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity.

Methods: This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification-negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%).

Results: WES analysis of these groups found pathogenic variants in 100.0% (3/3), 57.1% (12/21), and 68.2% (15/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes.

Conclusion: WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.

Keywords: congenital myopathies; muscular disorders; muscular dystrophies; mutational diversity; whole exome sequencing.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Patient enrollment workflow. Out of 161 patients with suspected genetic myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. MLPA for DMD and SMA identified causative variants in 60 and 31 patients, respectively. Other single gene tests and gene panels established a diagnosis in 18 patients. The remaining 46 patients underwent whole exome sequencing (WES) and were categorized into three groups: MLPA-negative DMD (n = 3), muscular dystrophies (MD; n = 21), and congenital myopathies (CM; n = 22).
FIGURE 2
FIGURE 2
Molecular diagnosis rate by disease group using whole exome sequencing. Molecular diagnoses were achieved in 65.2% of all patients analyzed (n = 30). The number of patients diagnosed in each disease group is indicated in parentheses.
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