Implementing a Tiered Genetic Testing Strategy for Muscular Dystrophies in Morocco: From Targeted Assays to Exome...

Area of Science:

• Genetics
• Neuromuscular Disorders
• Genomic Medicine

Background:

• Muscular dystrophies (MDs) are diverse inherited neuromuscular disorders.
• High consanguinity rates in Morocco suggest potential for recurrent genetic variants.
• The molecular basis of MDs in the Moroccan population is not fully understood.

Purpose of the Study:

• To investigate the genetic landscape of muscular dystrophies in Moroccan patients.
• To evaluate the effectiveness of a stepwise diagnostic approach combining targeted and broad genomic methods.
• To identify common and novel genetic variants associated with MDs in Morocco.

Main Methods:

• Analysis of 716 patients with suspected limb-girdle muscular dystrophy (LGMD) or dystrophinopathy over 32 years.
• Initial testing included multiplex PCR for DMD deletions and Sanger sequencing of SGCG:c.525delT.
• Unresolved cases underwent next-generation sequencing (NGS) via gene panels or whole-exome sequencing (WES).

Main Results:

• Multiplex PCR and Sanger sequencing resolved nearly half of the initial cases.
• Next-generation sequencing (NGS) identified frequent mutations in DMD, SGCG, SGCA, CAPN3, and FKRP.
• Several novel and recurrent variants suggest population-specific alleles in the Moroccan population.

Conclusions:

• The study highlights the genetic heterogeneity of MDs in Morocco.
• A combined approach of targeted and broad genomic strategies is effective for MD diagnosis.
• Further NGS is needed to fully characterize unresolved MD cases in this population.