Anoctaminopathies are a group of autosomal recessive skeletal muscle disorders with various clinical phenotypes, caused by anoctamin 5 (ANO5) gene mutations and the abnormal expression of ANO5 protein. Patients with recessive mutations in ANO5 present with variable symptoms ranging from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here, we describe the clinical, pathological, and molecular findings of two unrelated patients with ANO5-related muscular dystrophy (MD). Ninety-six histologically identified MD cases were subjected to next-generation sequencing using a customized panel of 54 genes (IIlumina Design Studio). Two patients were diagnosed with ANO5-related MD. One patient had a pathogenic homozygous mutation of c.1406G>A in exon 14, while the other patient had a novel heterozygous mutation of c.2141C>G in exon 19 of ANO5 gene. Both showed two different phenotypes (limb girdle MD and Miyoshi myopathy) and histomorphological patterns. Muscle biopsy of one patient in addition showed amyloid deposit in the walls of interstitial blood vessels. ANO5-related MD is a heterogeneous disease with different clinical phenotypes as well as genotypes. All muscle biopsies with unclassified muscular dystrophies should be subjected to Congo red stain. The results of this study suggest that screening for ANO5 gene should represent an early step in the diagnostic work-up of the patients with undiagnosed MD and persistent asymptomatic hyperCKemia, even when muscle biopsy histomorphology is normal.
Keywords: ANO5; HyperCKemia; Limb-girdle muscular dystrophy 2L; Miyoshi muscular dystrophy; Next-generation sequencing.