Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review
Anoctaminopathy-5 refers to a group of hereditary skeletal muscle or bone disorders due to mutations in the anoctamin 5 (ANO5)-encoding gene, <i>ANO5</i>. ANO5 is a 913-amino acid protein of the anoctamin family that functions predominantly in phospholipid scrambling and plays a key role...
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MDPI AG
2022-09-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/10/1736 |
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| author | Pannathat Soontrapa Teerin Liewluck |
| author_facet | Pannathat Soontrapa Teerin Liewluck |
| author_sort | Pannathat Soontrapa |
| collection | DOAJ |
| description | Anoctaminopathy-5 refers to a group of hereditary skeletal muscle or bone disorders due to mutations in the anoctamin 5 (ANO5)-encoding gene, <i>ANO5</i>. 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 <i>ANO5</i> 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. |
| first_indexed | 2024-03-09T12:17:20Z |
| format | Article |
| id | doaj.art-f3ac13c170eb44009ebcd4904fe99cfc |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T12:17:20Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-f3ac13c170eb44009ebcd4904fe99cfc2023-11-30T22:45:04ZengMDPI AGGenes2073-44252022-09-011310173610.3390/genes13101736Anoctamin 5 (ANO5) Muscle Disorders: A Narrative ReviewPannathat Soontrapa0Teerin Liewluck1Division of Neuromuscular Medicine, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USADivision of Neuromuscular Medicine, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USAAnoctaminopathy-5 refers to a group of hereditary skeletal muscle or bone disorders due to mutations in the anoctamin 5 (ANO5)-encoding gene, <i>ANO5</i>. 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 <i>ANO5</i> 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.https://www.mdpi.com/2073-4425/13/10/1736ANO5anoctamin 5anoctaminopathyLGMDLGMDR12limb–girdle muscular dystrophy |
| spellingShingle | Pannathat Soontrapa Teerin Liewluck Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review Genes ANO5 anoctamin 5 anoctaminopathy LGMD LGMDR12 limb–girdle muscular dystrophy |
| title | Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review |
| title_full | Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review |
| title_fullStr | Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review |
| title_full_unstemmed | Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review |
| title_short | Anoctamin 5 (ANO5) Muscle Disorders: A Narrative Review |
| title_sort | anoctamin 5 ano5 muscle disorders a narrative review |
| topic | ANO5 anoctamin 5 anoctaminopathy LGMD LGMDR12 limb–girdle muscular dystrophy |
| url | https://www.mdpi.com/2073-4425/13/10/1736 |
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