Novel Variants of ANO5 in Two Patients With Limb Girdle Muscular Dystrophy: Case Report

Front Neurol. 2022 Apr 8;13:868655. doi: 10.3389/fneur.2022.868655

PMID: 35463132

Matthew Katz, Fleur C Garton, Mark Davis, Robert D Henderson, Pamela A McCombe

Highlights: The results of this study broaden the genotypic range of ANO5 disease and support the diagnostic value of next-generation sequencing in individuals with limb girdle muscular dystrophy.

Abstract

Objective and Methods: Two unrelated adult patients presenting with Limb girdle muscular dystrophy who were found to have novel variants in ANO5 was reported. Both patients had prominent weakness of their proximal lower limbs with mild weakness of elbow flexion and markedly elevated creatine kinase. Next generation sequencing using a custom-designed neuromuscular panel was performed in both patients.

Results: In one patient, 336 genes were targeted for casual variants and in the other patient (using a later panel design), 464 genes were targeted. One patient was homozygous for a novel splice variant [c.294+5G>A; p.(Ala98Ins4*)] in ANO5. Another patient was compound heterozygous for two variants in ANO5; a common frameshift variant [c.191dupA; p.(Asn64fs)] and a novel missense variant [c.952G>C; p.(Ala318Pro)].

Conclusion: These findings support the utility of next generation sequencing in the diagnosis of patients presenting with a Limb girdle muscular dystrophy phenotype and extends the genotypic spectrum of ANO5 disease.

Keywords: ANO5, case report, limb girdle muscular dystrophy, next generation sequencing, novel variant.