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Review
. 2022 Sep 27;13(10):1736.
doi: 10.3390/genes13101736.

Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review

Pannathat Soontrapa  1   2 , Teerin Liewluck  1
Affiliations
Review

Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review

Pannathat Soontrapa et al. Genes (Basel). .

Abstract

Anoctaminopathy-5 refers to a group of hereditary skeletal muscle or bone disorders due to mutations in the anoctamin 5 (ANO5)-encoding gene, ANO5. ANO5 is a 913-amino acid protein of the anoctamin family that functions predominantly in phospholipid scrambling and plays a key role in the sarcolemmal repairing process. Monoallelic mutations in ANO5 give rise to an autosomal dominant skeletal dysplastic syndrome (gnathodiaphyseal dysplasia or GDD), while its biallelic mutations underlie a continuum of four autosomal recessive muscle phenotypes: (1). limb-girdle muscular dystrophy type R12 (LGMDR12); (2). Miyoshi distal myopathy type 3 (MMD3); (3). metabolic myopathy-like (pseudometabolic) phenotype; (4). asymptomatic hyperCKemia. ANO5 muscle disorders are rare, but their prevalence is relatively high in northern European populations because of the founder mutation c.191dupA. Weakness is generally asymmetric and begins in proximal muscles in LGMDR12 and in distal muscles in MMD3. Patients with the pseudometabolic or asymptomatic hyperCKemia phenotype have no weakness, but conversion to the LGMDR12 or MMD3 phenotype may occur as the disease progresses. There is no clear genotype-phenotype correlation. Muscle biopsy displays a broad spectrum of pathology, ranging from normal to severe dystrophic changes. Intramuscular interstitial amyloid deposits are observed in approximately half of the patients. Symptomatic and supportive strategies remain the mainstay of treatment. The recent development of animal models of ANO5 muscle diseases could help achieve a better understanding of their underlying pathomechanisms and provide an invaluable resource for therapeutic discovery.

Keywords: ANO5; LGMD; LGMDR12; MMD3; Miyoshi myopathy; anoctamin 5; anoctaminopathy; limb–girdle muscular dystrophy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of anoctamin 5 gene (ANO5) (A) and protein (ANO5) (B) displaying the relatively common mutations underlying autosomal recessive (AR) muscle disorders (more than 5 reported cases), autosomal dominant (AD) gnathodiaphyseal dysplasia (GDD), and combined muscle and bone phenotypes.
Figure 2
Figure 2
Clinical findings of a patient with ANO5 limb–girdle muscular dystrophy (LGMDR12) and recurrent rhabdomyolysis (A,B) and a patient with ANO5 distal myopathy of Miyoshi type (MMD3) (C). (A). Asymmetric atrophy of quadriceps. (B). Asymmetric atrophy of biceps brachii. (C). Asymmetric atrophy of gastrocnemius.
Figure 3
Figure 3
Histopathological findings in ANO5 muscle diseases. Congophilic deposits in intramuscular blood vessels and perimysium adjacent to perifascicular fibers are observed on Congo red stained section viewed under bright light (A), polarized light, (B) and rhodamine optics (C).
Figure 4
Figure 4
T1-weighted lower limb MRI in a patient with LGMDR12, calf atrophy and longstanding history of exercise intolerance and rhabdomyolysis showing asymmetrical fatty replacement of predominantly posterior lower limb compartment muscles, including bilateral adductor longus, long head of right biceps femoris, and bilateral semitendinosus (A) and bilateral medial gastrocnemius and parts of lateral gastrocnemius (B). AL—adductor longus, AM—adductor magnus, SM—semimembranosus, ST—semitendinosus, BFL—long head of biceps femoris, MG—medial gastrocnemius, LG—lateral gastrocnemius.
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This research received no external funding.