Clinical, Neurophysiological, Radiological, Pathological, and Genetic Features of Dysferlinopathy in Saudi Arabia

Norah Alharbi; Rawan Matar; Edward Cupler; Hindi Al-Hindi; Hatem Murad; Iftteah Alhomud; Dorota Monies; Ali Alshehri; Mossaed Alyahya; Brian Meyer; Saeed Bohlega

doi:10.3389/fnins.2022.815556

Clinical, Neurophysiological, Radiological, Pathological, and Genetic Features of Dysferlinopathy in Saudi Arabia

Front Neurosci. 2022 Feb 22:16:815556. doi: 10.3389/fnins.2022.815556. eCollection 2022.

Authors

Norah Alharbi¹, Rawan Matar², Edward Cupler³, Hindi Al-Hindi⁴, Hatem Murad⁵, Iftteah Alhomud⁵, Dorota Monies⁶, Ali Alshehri⁵, Mossaed Alyahya⁵, Brian Meyer⁶, Saeed Bohlega⁵

Affiliations

¹ Department of Clinical Science, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.
² Salmaniya Medical Complex, Manama, Bahrain.
³ Department of Neuroscience, King Faisal Specialist Hospital, and Research Center, Jeddah, Saudi Arabia.
⁴ Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁵ Department of Neuroscience, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
⁶ Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Abstract

Background: To characterize the phenotypic, neurophysiological, radiological, pathological, and genetic profile of 33 Saudi Arabian families with dysferlinopathy.

Methods: A descriptive observational study was done on a cohort of 112 Saudi Arabian families with LGMD. Screening for the Dysferlin (DYSF) gene was done in a tertiary care referral hospital in Saudi Arabia. Clinical, Neurophysiological, Radiological, Pathological, and Genetic findings in subjects with dysferlin mutation were the primary outcome variables. Statistical analysis was done by Epi-info.

Results: 33 out of 112 families (29.46%) registered in the LGMD cohort had Dysferlinopathy. 53 subjects (28 males, 52.83%) from 33 families were followed up for various periods ranging from 1 to 28 years. The mean age of onset was 17.79 ± 3.48 years (Range 10 to 25 years). Miyoshi Myopathy phenotype was observed in 50.94% (27 out of 53), LGMDR2 phenotype in 30.19% (16 out of 53), and proximodistal phenotype in 15.09% (8 out of 53) of the subjects. Loss of ambulation was observed in 39.62% (21 out of 53 subjects). Electrophysiological, Radiological, and histopathological changes were compatible with the diagnosis. Mean serum Creatinine Kinase was 6,464.45 ± 4,149.24 with a range from 302 to 21,483 IU/L. In addition, 13 dysferlin mutations were identified two of them were compound heterozygous. One founder mutation was observed c.164_165insA in 19 unrelated families.

Conclusion: The prevalence of Dysferlinopathy was 29.46% in the native Saudi LGMD cohort. It is the most prevalent subtype seconded by calpainopathy. The clinical course varied among the study subjects and was consistent with those reported from different ethnic groups. One founder mutation was identified. Initial screening of the founder mutations in new families is highly recommended.

Keywords: DYSF gene; LGMD2B; Miyoshi myopathy; Saudi Arabia; dysferlin; dysferlinopathy; limb-girdle muscular dystrophies (LGMD); neurophysiological profile.