Genetic Analysis of ۴۰ MLPA-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing

This manuscript aimed to determine the underlying point mutations causing DMD in a heterogeneous groupof Iranian patients, who are clinically suspected. Whole-Exome sequencing was utilized to detect diseasecausingvariants in ۴۰ MLPA-negative DMD patients. Disease-causing variants were detected in the DMDgene in ۳۶/۴۰ of the patients (۹۰%), and ۴/۴۰ of them (۱۰%) remained undiagnosed. WES analysis revealedthat nonsense mutation was the most common type in our study (۲۳/۳۶ of the cases). Besides, ۱۲/۳۶ of thecases had frameshift mutation, and one of the patients had a likely pathogenic splice variant in the DMDgene. Carrier testing revealed that ۲۱/۴۰ of the mothers had the identified variant. Therefore, most mutationswere inherited (۵۸.۳%), while ۱۹/۴۰ were de novo (۴۱. ۷%). The present study has demonstrated theimportance of performing WES to detect disease-causing point mutations in MLPA-negative DMD patientsand to identify carrier females. Due to regulatory challenges, the clinical development of therapeuticapproaches is time-consuming and may not be available to all patients shortly. Therefore, it appears that thetechniques used to accurately detect mutations in carrier mothers are a more efficient solution to prevent theincreased prevalence of DMD.

Keywords:

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