Genetic Analysis of Forty Mlpa-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing Publisher Pubmed



Zamani GR¹ ; Mohammadi MF² ; Tavasoli AR^{1, 6} ; Ashrafi MR¹ ; Hosseinpour S³ ; Ghabeli H¹ ; Pourbakhtyaran E¹ ; Haghighi R¹ ; Hosseiny SMM⁴ ; Mohammadi P⁵ ; Heidari M¹
Source: Journal of Molecular Neuroscience Published:2022

Abstract

This manuscript aimed to determine the underlying point mutations causing Duchenne muscular dystrophy (DMD) in a heterogeneous group of Iranian patients, who are clinically suspected. Whole-exome sequencing was utilized to detect disease-causing variants in 40 MLPA-negative DMD patients. Disease-causing variants were detected in the DMD gene in 36/40 of the patients (90%), and 4/40 of them (10%) remained undiagnosed. WES analysis revealed that nonsense variant was the most common type in our study (23/36 of the cases). Besides, 12/36 of the cases had frameshift variant, and one of the patients had a likely pathogenic splice variant in the DMD gene. Carrier testing revealed that 21/40 of the mothers had the identified variant. Therefore, most variants were inherited (58.3%), while 19/40 were de novo (41. 7%). The present study has demonstrated the importance of performing WES to detect disease-causing point mutations in MLPA-negative DMD patients and to identify carrier females. Due to regulatory challenges, the clinical development of therapeutic approaches is time-consuming and may not be available to all patients shortly. Therefore, it appears that the techniques used to accurately detect disease-causing variants in carrier mothers are a more efficient solution to prevent the increased prevalence of DMD. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.