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Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

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ANO5-Related Muscle Diseases

Synonym: Anoctaminopathy

, MSc, , MD, PhD, and , MD, PhD.

Author Information
, MSc
Neuromuscular Research Unit
University of Tampere
Tampere, Finland
, MD, PhD
Neuromuscular Research Unit
University of Tampere
Tampere, Finland
, MD, PhD
Neuromuscular Research Unit
University of Tampere
Tampere, Finland

Initial Posting: .

Summary

Disease characteristics. The spectrum of ANO5-related muscle diseases is a continuum that ranges from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. The most typical presentation is limb-girdle muscular dystrophy type 2L (LGMD2L) with late-onset proximal lower-limb weakness (mean onset age 35 years; range 15-70 years). Less common is Miyoshi-like disease or Miyoshi muscular dystrophy 3 with early adult-onset calf distal myopathy (age 20 to 25 years). Incidental hyperCKemia may be present even earlier. Females have milder disease manifestations than males. Initial symptoms are walking difficulties, reduced sports performance, and difficulties in standing on toes as well as nonspecific exercise myalgia and/or burning sensation in the calf muscles. Muscle weakness and atrophy are frequently asymmetric. Bulbar or respiratory symptoms have not been reported. Disease progression is slow in both the LGMD and distal forms; ambulation is preserved until very late in the disease course.

Diagnosis/testing. The diagnosis is based on clinical findings, elevated serum CK concentration, and molecular genetic testing of ANO5.

Management. Treatment of manifestations: No definitive treatments for the limb-girdle muscular dystrophies exist. Management is tailored to each individual. To prolong survival and improve quality of life the following are suggested: weight control to avoid obesity, physical therapy and stretching exercises to promote mobility and prevent contractures, and use of mechanical aids to help ambulation and mobility. The need for orthoses or other assistive devices varies individually; hyperextension of the knee can be treated by splinting.

Surveillance: For persons with muscle weakness: evaluate muscle strength and functional status every six to 12 months. For asymptomatic persons: evaluate less frequently.

Agents/circumstances to avoid: Heavy muscle force training of weak muscles. The use of statins, which can induce muscle pain and worsen muscle weakness, requires extra monitoring of clinical status especially at the beginning of treatment.

Genetic counseling. ANO5-related muscle diseases are inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family have been identified. Requests for prenatal testing for conditions such as the ANO5-related muscle diseases that do not affect intellect and are typically adult onset are not common.

GeneReview Scope

ANO5-Related Muscle Diseases: Included Disorders
  • Limb-Girdle muscular dystrophy type 2L
  • Miyoshi muscular dystrophy 3

For synonyms and outdated names see Nomenclature.

Diagnosis

Clinical Diagnosis

The spectrum of ANO5-related muscle diseases is a continuum that ranges from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. The most typical presentation is limb-girdle muscular dystrophy type 2L (LGMD2L) with late-onset proximal lower-limb weakness (mean onset age 35 years; range 15-70 years) [Bolduc et al 2010, Hicks et al 2011, Penttilä et al 2012]. Less common is Miyoshi-like disease or Miyoshi muscular dystrophy 3 with early adult-onset calf distal myopathy (age 20 to 25 years) [Mahjneh et al 2010, Hicks et al 2011, Penttilä et al 2012].

Adult-onset, asymmetric muscle weakness and atrophy, especially in thigh muscles, are characteristic features in ANO5-related muscle diseases (Figure 1).

Figure 1

Figure

Figure 1. Asymmetric atrophy of the muscles of the left calf in an individual with an ANO5 mutation

Females are generally less severely affected than males [Penttilä et al 2012].

EMG reveals myopathic changes with scattered necrotic fibers; however, it can be normal in mildly affected individuals [Penttilä et al 2012].

CT and MRI show fatty degeneration of the gastrocnemius medialis muscle in most affected individuals. As the disease progresses, the soleus and posterior thigh muscles are frequently involved (Figure 2) [Mahjneh et al 2010, Hicks et al 2011, Magri et al 2012, Penttilä et al 2012].

Figure 2

Figure

Figure 2.

A. Fatty degenerative changes in posterior thigh muscles in the left vastus medialis and intermedius muscles

B. Fatty degenerative changes in the medial gastrocnemius (left greater than right) and in the left (more...)

Testing

Serum CK concentration is markedly elevated (≥2-3x – and usually 10-50x – the upper limit of normal). Although serum CK concentration may vary between measurements in the same individual, normal concentrations have not been reported, even in the elderly.

Muscle biopsy shows scattered necrotic fibers or nonspecific myopathic or dystrophic findings [Hicks et al 2011, Penttilä et al 2012].

Molecular Genetic Testing

Gene. ANO5 is the only gene in which mutations are known to cause ANO5-related muscle diseases.

Table 1. Summary of Molecular Genetic Testing Used in ANO5-Related Muscle Diseases

Gene 1Test MethodMutations Detected 2Mutation Detection Frequency by Test Method 3
ANO5Sequence analysis 4Sequence variants 5Unknown 6
Deletion/duplication analysis 7Exonic or whole-gene deletions Unknown; none reported 8

1. See Table A. Genes and Databases for chromosome locus and protein name.

2. See Molecular Genetics for information on allelic variants

3. The ability of the test method used to detect a mutation that is present in the indicated gene

4. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

5. The most common mutations in northern European populations are c.191dupA in exon 5 and c.2272C>T in exon 20. To date, in publications of ANO5-related muscle diseases in persons of European origin, sequence analysis of exons 5 and 20 reveals at least one mutation in the majority (45/53) [Bolduc et al 2010, Hicks et al 2011, Bouquet et al 2012, Magri et al 2012, Milone et al 2012, Penttilä et al 2012, Schessl et al 2012]. Detecting the other mutation often requires sequence analysis of the whole gene.

6. Sequence analysis of all the exons and exon-intron regions detects all reported mutations [Bolduc et al 2010, Deschauer et al 2011, Hicks et al 2011, Magri et al 2012, Milone et al 2012, Penttilä et al 2012, Schessl et al 2012]. It is unknown if there are mutations that cannot be detected by sequence analysis.

7. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

8. No deletions or duplications of ANO5 have been reported to cause limb-girdle muscular dystrophy type 2L.

Testing Strategy

To confirm/establish the diagnosis in a proband with findings suggestive of ANO5-related muscle diseases, perform molecular genetic testing. Two strategies are:

Single-gene testing

Multi-gene testing

  • Because the limb-girdle muscular dystrophy (LGMD) phenotype of ANO5-related muscle diseases may not be distinguishable from LGMD caused by mutations in other genes, clinicians may consider using a multi-gene limb-girdle muscular dystrophy panel that includes ANO5. Note that multi-gene panels vary by methods used and genes included; thus, the ability of a panel to detect a causative mutation(s) in any given individual also varies.

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder.

Predictive testing for at-risk asymptomatic adult family members requires prior identification of the disease-causing mutations in the family.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Clinical Description

Natural History

The spectrum of ANO5-related muscle diseases is a continuum ranging from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. The most typical presentation is late-onset proximal lower-limb weakness (also called limb-girdle muscular dystrophy type 2L) [Bolduc et al 2010, Hicks et al 2011, Penttilä et al 2012] (Table 2).Less common is early adult-onset calf distal myopathy (also called Miyoshi muscular dystrophy 3) [Mahjneh et al 2010, Hicks et al 2011, Penttilä et al 2012].

Females have milder disease manifestations than males [Bolduc et al 2010, Hicks et al 2011, Magri et al 2012, Penttilä et al 2012].

Onset of the proximal weakness in the limb-girdle muscular dystrophy (LGMD) form is in the fourth or fifth decade (age range 15-70 years); onset of calf weakness in the distal form is around age 20 years. Incidental hyperCKemia may be present even earlier. Initial symptoms are walking difficulties, reduced sports performance, and difficulties in standing on toes as well as nonspecific exercise myalgia and/or burning sensation in the calf muscles [Bolduc et al 2010, Hicks et al 2011, Penttilä et al 2012].

In the limb-girdle muscular dystrophy form, muscle weakness is mainly proximal and more pronounced in the lower limbs; however, many affected individuals also have proximal upper-limb involvement.

In the distal myopathy form, calf hypertrophy and exercise myalgia can occur before apparent weakness and later calf atrophy. Clinical manifestations can be mild or subjectively nonexistent even with clear changes observed on muscle imaging. Individuals with distal onset may have proximal lower-limb weakness in the later stages of the disease. Distal upper-limb weakness has not been reported.

In most affected males muscle weakness is apparent with variable severity whereas in affected females the symptoms are consistently milder. Of 17 affected females reported to date, only five have had detectable muscle weakness and the others have had only hyperCKemia with or without myalgia [Bolduc et al 2010, Hicks et al 2011, Magri et al 2012, Milone et al 2012, Penttilä et al 2012, Schessl et al 2012].

Muscle weakness and atrophy are frequently asymmetric (Figure 1).

Table 2. The LGMD2L Phenotype

Clinical Characteristic# of Individuals
Increased creatine kinase value (>10x)20/20
Proximal lower-limb weakness20/20
Adult onset (>20 years)19/20
Muscle atrophy:19/20
  • Quadriceps/hamstrings
15/20
  • Calf
14 (8 1) /20
  • Quadriceps/hamstrings and calf
10/20
  • Upper-limb (mainly biceps)
7/20
Asymmetry of muscle weakness or atrophy18/20
Distal lower-limb weakness:17/20
  • Mild
13/20
  • Moderate to severe
5/20
Upper-limb proximal weakness:13/20
  • Mild
11/20
  • Moderate to severe
2/20
Good sports performance in presymptomatic period8/20
Knee hyperextension7/20
Scapular winging6/20
Restriction/loss of ambulation4/20
Contractures4/20
Myoglobinuria3/20

From Hicks et al [2011]

1. Medial part

In 19 individuals with ANO5-related muscle diseases who underwent systematic cardiac investigations, two had dilated cardiomyopathy and three had left ventricular dilatation [Wahbi et al 2012]. Bulbar or respiratory symptoms have not been reported.

Disease progression is slow in both the LGMD and distal form; ambulation is preserved until very late in the disease course. Most affected individuals remain ambulatory without assistance for decades. Life span appears to be normal.

Genotype-Phenotype Correlations

Although genotype-phenotype correlations were initially suggested, no correlations were detected in a large patient cohort [Penttilä et al 2012].

Penetrance

Penetrance of disease manifestations in those with biallelic ANO5 mutations depends on the clinical findings used to determine presence of clinical manifestations, age, and sex.

In early stages of the disease (before evidence of subclinical findings on muscle MRI of the disease), hyperCKemia may be the only sign of the disease.

Based on subclinical findings on muscle imaging in affected individuals in the families studied to date, the penetrance in those with biallelic confirmed pathogenic mutations is complete; however, expressivity is variable as the age of onset varies significantly, and females, who are less severely affected than males, may remain symptom free at a later age than males [Penttilä et al 2012].

Anticipation

Anticipation is not known to occur in ANO5-related muscle diseases.

Nomenclature

Miyoshi muscular dystrophy 3 may also be referred to as non-dysferlin Miyoshi muscular dystrophy or MMD3.

Prevalence

ANO5-related muscle diseases have been estimated to be one of the most common causes of limb-girdle muscular dystrophy. Prevalence in Finland is as high as 2:100,000 [Penttilä et al 2012]; in the North of England it has been estimated at 0.26:100,000 [Hicks et al 2011].

Differential Diagnosis

Limb-girdle muscular dystrophy. The differential diagnosis of ANO5-related muscle diseases includes all the limb-girdle muscular dystrophies (see Limb-Girdle Muscular Dystrophy Overview).

LGMD multi-gene panels may include testing for a number of the disorders discussed in this section.

Note: The genes included and the methods used in multi-gene panels vary by laboratory and over time; a panel may not include a specific gene of interest.

Of particular note is dysferlinopathy, which includes a spectrum of muscle disease that is characterized by two main phenotypes: Miyoshi myopathy with primarily distal weakness and limb-girdle muscular dystrophy type 2B (LGMD2B) with primarily proximal weakness. Miyoshi myopathy (median age of onset 19 years) is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared. LGMD2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles in adolescence or young adulthood, with slow progression.

Distal myopathies. For the differential diagnosis of distal myopathies, the combination of muscle MRI, muscle pathology, and mode of inheritance is useful in reducing the need for molecular genetic diagnostics [Udd 2012].

Table 3. Distal Myopathies

Disease NameMean Age at Onset (Years)Initial Muscle Group InvolvedSerum Creatine Kinase ConcentrationMuscle BiopsyGene (Locus) 1
Autosomal dominant
Welander distal myopathy>40Distal upper limbs (finger and wrist extensors)Normal or slightly increasedRimmed vacuoles(2p13)
Udd distal myopathy>35Anterior compartment in legs± Rimmed vacuolesTTN
Markesbery-Griggs late-onset distal myopathy>40Vacuolar and myofibrillar myopathy(ZASP) LDB3
Distal myotilinopathy>40Posterior > anterior in legsSlightly increasedVacuolar and myofibrillarMYOT
Laing early-onset distal myopathy (MPD1)<20Anterior compartment in legs and neck flexorsNormal to (rarely) moderately increasedType 1 fiber atrophy in tibial anterior muscles; disproportion in proximal musclesMYH7
Distal myopathy with vocal cord and pharyngeal signs (MPD2)35-60Asymmetric lower leg and hands; dysphonia1-8 timesRimmed vacuolesMATR3
Distal myopathy with pes cavus and areflexia15-50Anterior and posterior lower leg; dysphonia and dysphagia2-6 timesDystrophic, rimmed vacuoles(19p13)
New Finnish distal myopathy (MPD3)>30Hands or anterior lower leg1-4 timesDystrophic; rimmed vacuoles; eosinophilic inclusions(8p22-q11 and 12q13-q22)
Autosomal recessive
Nonaka early-adult-onset distal myopathy15-20Anterior compartment in legs<10 timesRimmed vacuolesGNE
Miyoshi early adult-onset myopathyPosterior compartment in legs>10 timesMyopathic changesDYSF

Udd & Griggs [2001]

1. Locus given only if the gene is not known

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg, an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with ANO5-related muscle diseases, the following evaluations are recommended:

  • Neurologic evaluation and manual muscle force measurement to establish a baseline for future assessment of disease progression and the possible need for assistive devices.
  • Muscle imaging (CT or MRI) to identify the pattern of affected muscles in detail
  • Medical genetics consultation

Treatment of Manifestations

The need for orthoses or other assistive devices varies individually. Most patients remain ambulatory without assistance for decades.

No definitive treatments for the limb-girdle muscular dystrophies exist. Management is tailored to each individual and each specific subtype. Management to prolong survival and improve quality of life includes weight control to avoid obesity, physical therapy and stretching exercises to promote mobility and prevent contractures, and use of mechanical aids to help ambulation and mobility.

Hyperextension of the knee can be treated by splinting [Hicks et al 2011].

Surveillance

For persons with muscle weakness, evaluate muscle strength and functional status every six to 12 months.

For asymptomatic persons, evaluate less frequently.

Agents/Circumstances to Avoid

Heavy muscle force training of weak muscles should be avoided as very high levels of CK have been measured after strenuous exercise [Milone et al 2012, Penttilä et al 2012].

The use of statins, which can induce muscle pain and worsen muscle weakness, requires extra monitoring of clinical status especially at the beginning of treatment.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

ANO5-related muscle diseases are inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected individual are obligate heterozygotes (i.e., carriers of one mutant allele).
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. The offspring of an individual with an ANO5-related muscle disease are obligate heterozygotes (carriers) for a disease-causing mutation in ANO5.

Other family members. Each sib of the proband’s parents is at a 50% risk of being a carrier.

Carrier Detection

Carrier testing for at-risk family members is possible if the disease-causing mutations in the family have been identified.

Related Genetic Counseling Issues

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

If the disease-causing mutations have been identified in the family, prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed at ~15-18 weeks’ gestation) or chorionic villus sampling (usually performed at ~10-12 weeks’ gestation).

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Requests for prenatal testing for conditions which (like the ANO5-related muscle diseases) do not affect intellect and are typically adult onset are not common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although decisions about prenatal testing are the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutations have been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Genetic and Rare Diseases Information Center (GARD)
    PO Box 8126
    Gaithersburg MD 20898-8126
    Phone: 888-205-2311 (toll-free); 888-205-3223 (toll-free TTY)
    Fax: 301-251-4911
    Email: GARDinfo@nih.gov
  • Muscular Dystrophy Association - Canada
    2345 Yonge Street
    Suite 900
    Toronto Ontario M4P 2E5
    Canada
    Phone: 866-687-2538 (toll-free); 416-488-0030
    Fax: 416-488-7523
    Email: info@muscle.ca
  • Muscular Dystrophy Association - USA (MDA)
    3300 East Sunrise Drive
    Tucson AZ 85718
    Phone: 800-572-1717
    Email: mda@mdausa.org
  • Muscular Dystrophy Campaign
    61 Southwark Street
    London SE1 0HL
    United Kingdom
    Phone: 0800 652 6352 (toll-free); +44 0 020 7803 4800
    Email: info@muscular-dystrophy.org

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. ANO5-Related Muscle Diseases: Genes and Databases

Locus NameGene SymbolChromosomal LocusProtein NameLocus SpecificHGMD
LGMD2LANO511p14​.3Anoctamin-5ANO5 homepage - Leiden Muscular Dystrophy pages
Human and Clinical Genetics(ANO5)
ANO5

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for ANO5-Related Muscle Diseases (View All in OMIM)

608662ANOCTAMIN 5; ANO5
611307MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2L; LGMD2L
613319MIYOSHI MUSCULAR DYSTROPHY 3; MMD3

Gene structure. ANO5 is predicted to produce several alternatively spliced transcripts that encode different isoforms; however, only two transcripts have been described. The major transcript variant expressed in muscle (NM_213599.2) has 22 exons and 6661 base pairs and codes for a 913-amino acid protein (NP_998764.1), whereas the other transcript variant (NM_001142649.1) codes for a 912-amino acid product. For a detailed summary of gene and protein information, see Table A, Gene Symbol.

Benign allelic variants. In exon 10, the common benign variant c.966A>T (dbSNP reference rs7481951) has a frequency of 35%, according to 1000 Genomes.

Pathogenic allelic variants. A large number of recessive ANO5 mutations are known. The mutations are distributed evenly along the gene without any clear mutational hotspot.

The most common mutation in European populations, c.191dupA, causes a frameshift that leads to premature truncation of the protein (p.Asn64LysfsTer15).

Other small frameshift insertions and deletions include: c.1627dupA and c.2311_2312delCA.

Most mutations seem to be missense mutations, like the common variant c.2272C>T and the rarer variants c.242A>G, c.692G>T, c.1643C>T, c.1733T>C, and c.2101A>G.

Several mutations affect splicing (e.g., c.1295C>G and c.1407+5G>A).

Table 4. Selected ANO5 Allelic Variants

Class of Variant AlleleDNA Nucleotide Change Protein Amino Acid ChangeReference Sequences
Benignc.966A>Tp.Leu322PheNM_213599​.2
NP_998764​.1
Pathogenicc.191dupA 1p.Asn64LysfsTer15
c.242A>Gp.Asp81Gly
c.692G>Tp.Gly231Val
c.1295C>Gp.Ala432GlyfsTer49
c.1407+5G>Ap.Glu445_Trp469del
c.1627dupAp.Met543AsnfsTer11
c.1643C>Tp.Thr548Ile
c.1733T>Cp.Phe578Ser
c.2101A>Gp.Asn701Asp
c.2272C>T 1p.Arg758Cyc
c.2311_2312delCAp.Gln771AlafsTer8
c.1066T>Cp.Cys356Arg
c.1066T>Gp.Cys356Gly
c.1538C>Tp.Thr513Ile

Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1. The most common mutations in northern European populations are c.191dupA in exon 5 and c.2272C>T in exon 20.

Normal gene product. The major isoform in muscle consists of 913 amino acids. The protein anoctamin-5 has eight transmembrane domains, a re-entrant loop (a structural motif that goes only halfway through the membrane and then turns back to the side from which it originates) between the fifth and sixth transmembrane domain, and a DUF590 domain of unknown function. The function of anoctamin-5 is not known.

Abnormal gene product. Some pathogenic allelic variants leading to ANO5-related muscle diseases cause a change in one amino acid and some lead to premature truncation or aberrant splicing. How the abnormal gene products cause disease is not fully understood.

References

Literature Cited

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Chapter Notes

Revision History

  • 29 November 2012 (me) Review posted live
  • 19 July 2012 (sp) Original submission
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