1st International and 10th National Iranian Conference on Bioinformatics

Genetic Analysis of 40 MLPA-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing

Paper ID : 1112-ICB10

Authors:

Mohammad Farid mohammadi *

Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

Abstract:

Abstract
This manuscript aimed to determine the underlying point mutations causing 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 mutation was the most common type in our study (23/36 of the cases). Besides, 12/36 of the cases had frameshift mutation, 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 mutations 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 mutations in carrier mothers are a more efficient solution to prevent the increased prevalence of DMD.

Keywords:

Duchenne muscular dystrophy. Multiplex ligation-dependent probe amplification. Whole-exome sequencing, Dystrophin

Status : Paper Accepted (Poster Presentation)