Hyperckemia and myalgia are common presentations of anoctamin‐5‐related myopathy in French patients

Papadopoulos, Constantinos; Laforêt, Pascal; Nectoux, Juliette; Stojkovic, Tanya; Wahbi, Karim; Carlier, Robert‐Yves; Carlier, Pierre; Léonard-Louis, Sarah; Leturcq, F.; Romero, N.; Eymard, B.; Béhin, Anthony

doi:10.1002/mus.25608

Cited by 31 publications

(45 citation statements)

References 20 publications

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“…Unlike other LGMDs, asymmetric weakness is relatively common in these 2 muscular dystrophies, especially anoctaminopathy‐5, in which prominent asymmetrical atrophy of the quadriceps femoris and biceps brachii is the diagnostic hallmark . Patients with dysferlinopathy or anoctaminopathy‐5 may develop exercise intolerance or rhabdomyolysis preceding the fixed weakness . Myalgia and hyperCKemia without apparent weakness was a common presentation in a French cohort with anoctaminopathy‐5 .…”

Section: Lgmd Subgroupsmentioning

confidence: 96%

“…95,96 Patients with dysferlinopathy or anoctaminopathy-5 may develop exercise intolerance or rhabdomyolysis preceding the fixed weakness. [96][97][98][99][100] Myalgia and hyperCKemia without apparent weakness was a common presentation in a French cohort with anoctaminopathy-5. 100 Female patients with anoctaminopathy-5 generally have a milder phenotype compared with males.…”

Section: Muscular Dystrophies With Defective Membranementioning

confidence: 99%

“…[96][97][98][99][100] Myalgia and hyperCKemia without apparent weakness was a common presentation in a French cohort with anoctaminopathy-5. 100 Female patients with anoctaminopathy-5 generally have a milder phenotype compared with males. 101 Significant cardiopulmonary involvement in these 2 muscular dystrophies with defective membrane repair is uncommon but has been reported in various studies.…”

Section: Muscular Dystrophies With Defective Membranementioning

confidence: 99%

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Untangling the complexity of limb‐girdle muscular dystrophies

Liewluck

Milone

2018

Muscle and Nerve

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The limb-girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous, autosomal inherited muscular dystrophies with a childhood to adult onset, manifesting with hip- and shoulder-girdle muscle weakness. When the term LGMD was first conceptualized in 1954, it was thought to be a single entity. Currently, there are 8 autosomal dominant (LGMD1A-1H) and 26 autosomal recessive (LGMD2A-2Z) variants according to the Online Mendelian Inheritance in Man database. In addition, there are other genetically identified muscular dystrophies with an LGMD phenotype not yet classified as LGMD. This highlights the entanglement of LGMDs, which represents an area in continuous expansion. Herein we aim to simplify the complexity of LGMDs by subgrouping them on the basis of the underlying defective protein and impaired function. Muscle Nerve 58: 167-177, 2018.

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Section: Lgmd Subgroupsmentioning

confidence: 96%

Section: Muscular Dystrophies With Defective Membranementioning

confidence: 99%

Section: Muscular Dystrophies With Defective Membranementioning

confidence: 99%

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Untangling the complexity of limb‐girdle muscular dystrophies

Liewluck

Milone

2018

Muscle and Nerve

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“…ANO5 encodes a putative calcium‐activated chloride channel, known as anoctamin 5, which plays a role in muscle cell membrane fusion and repair . Recessive mutations in ANO5 cause limb‐girdle muscular dystrophy type 2L (LGMD2L), Miyoshi‐like distal myopathy (MMD3) and serum creatine kinase (CK) increase with variable exercise intolerance . Dominant variants have been associated with the skeletal disorder gnathodiaphyseal dysplasia (GDD) …”

Section: Introductionmentioning

confidence: 99%

“…The frequency of LGMD2L, the most common presentation of anoctaminopathy, in LGMD cohorts has been reported from 2% in Italian population and 7% in US population to around 25% in UK and Finland populations . Additionally, many other patients have been identified with non‐LGMD phenotypes, and up to 50% of patients harboring ANO5 mutations may have a distal myopathy or an isolated hyperCKemia as initial presentation . A common mutation (c.191dupA), for which is suggested to be the result of a founder effect on Northern Europeans, and another variant (c.2272C > T), especially common in the Finnish population, are considered the most frequent mutations in patients with anoctaminopathy, but many other variants have been described …”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular findings in a cohort of ANO5‐related myopathy

Silva

Coimbra-Neto

Souza

et al. 2019

Ann Clin Transl Neurol

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Objective ANO5‐related myopathy is an important cause of limb‐girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. Methods A national cross‐sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. Results Thirty‐seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss‐of‐function variants were not associated with specific phenotypes. Interpretation We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.

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A Pilot Genome‐Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH

et al. 2019

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A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome‐wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (P < 1 × 10-4) with NASH resolution. A sentinel SNP, rs75508464, near CELA3B on chromosome 1 was associated with NASH resolution, improvement in the nonalcoholic fatty liver disease activity score, portal inflammation, and fibrosis. Among individuals carrying this allele, 83% achieved NASH resolution with OCA compared with only 33% with placebo. Eight regions on chromosomes 1, 2, 3, 11, 13, and 18 had multiple SNPs associated with fibrosis improvement; of these, rs12130403 near TDRD10 on chromosome 1 was also associated with improvement in NASH and portal inflammation, and rs4073431 near ANO3 on chromosome 11 was associated with NASH resolution and improvement in steatosis. Multiple SNPs on chromosome 11 had suggestive association with pruritus, with rs1379650 near ANO5 being the top SNP. Conclusion: We identified several variants that may be associated with histological improvement and pruritus in individuals with NASH receiving OCA. The rs75508464 variant near CELA3B may have the most significant effect on NASH resolution in those receiving OCA.

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Hyperckemia and myalgia are common presentations of anoctamin‐5‐related myopathy in French patients

Abstract: Asymptomatic, sometimes mild hyperCKemia or exercise intolerance is a presentation of ANO5-related myopathy and may remain isolated or precede muscle weakness by many years. Muscle Nerve 56: 1096-1100, 2017.

Cited by 31 publications

References 20 publications

Untangling the complexity of limb‐girdle muscular dystrophies

Untangling the complexity of limb‐girdle muscular dystrophies

Clinical and molecular findings in a cohort of ANO5‐related myopathy

A Pilot Genome‐Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH

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