New Assay May Help to Diagnose Limb Girdle Muscular Dystrophy in Most Patients

A newly developed neurological panel assay can accurately determine the precise gene mutations affecting patients with limb girdle muscular dystrophy (LGMD) and other myopathies, potentially improving their treatment, according to researchers in Saudi Arabia.

The study, “A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies,” was published in the scientific journal Human Genomics.

To evaluate whether this assay could be a reliable diagnostic test, the team of researchers, led by Dr. Saeed Bohlega at King Faisal Specialist Hospital and Research Center, genetically screened 50 random families, not previously studied genetically, with a panel covering 759 genes associated with neurological disorders. All patients had muscle weakness affecting the pelvic and shoulder girdle, and muscle biopsies showed dystrophic or myopathic changes.

Results demonstrated that the panel was able to identify disease-causing mutations in 38 of the 50 families (76%). While 34 families had mutations in the LGMD-related genes, four had variants not typically associated with LGMD.

People in the majority of these families (37 out of 38) had recessive inheritance, meaning that affected individuals had two copies of the disease-causing gene. This was expected since there was a high rate of co-sanguinity in the families.

There were seven different subtypes of LGMD2 in the families studied. Mutations in the DYSF gene were the most common, followed by mutations in the CAPN3 gene and the FKRP gene. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation, such as the ALG2 gene, as well as rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1).

LGMD is a large group of conditions, and around a fourth of all patients do not receive a precise genetic diagnosis. Being able to offer a genetic diagnosis means that clinicians can better predict how the condition will progress, and the best possible care and management of the disease can be offered to patients.

“We believe that the majority of LGMD patients can be diagnosed using this new very powerful genomic tool,” the authors concluded.