Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recently described human anion channel Anoctamin (ANO) protein family comprises at least ten members, many of which have been shown to correspond to calcium-activated chloride channels. To date, the only reported human mutations in this family of genes are dominant mutations in ANO5 (TMEM16E, GDD1) in the rare skeletal disorder gnathodiaphyseal dysplasia. We have identified recessive mutations in ANO5 that result in a proximal limb-girdle muscular dystrophy (LGMD2L) in three French Canadian families and in a distal non-dysferlin Miyoshi myopathy (MMD3) in Dutch and Finnish families. These mutations consist of a splice site, one base pair duplication shared by French Canadian and Dutch cases, and two missense mutations. The splice site and the duplication mutations introduce premature-termination codons and consequently trigger nonsense-mediated mRNA decay, suggesting an underlining loss-of-function mechanism. The LGMD2L phenotype is characterized by proximal weakness, with prominent asymmetrical quadriceps femoris and biceps brachii atrophy. The MMD3 phenotype is associated with distal weakness, of calf muscles in particular. With the use of electron microscopy, multifocal sarcolemmal lesions were observed in both phenotypes. The phenotypic heterogeneity associated with ANO5 mutations is reminiscent of that observed with Dysferlin (DYSF) mutations that can cause both LGMD2B and Miyoshi myopathy (MMD1). In one MMD3-affected individual, defective membrane repair was documented on fibroblasts by membrane-resealing ability assays, as observed in dysferlinopathies. Though the function of the ANO5 protein is still unknown, its putative calcium-activated chloride channel function may lead to important insights into the role of deficient skeletal muscle membrane repair in muscular dystrophies.
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PMID:Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. 2009 97

We report a 45year-old patient with an asymmetrical proximal muscle weakness affecting the quadriceps muscle of the right leg starting at the age of 32years. CK was 25-fold increased. MRI of the legs showed signs of fatty degeneration more pronounced in the right side. Biopsy of a thigh muscle showed dystrophic pattern and amyloid deposition in blood vessel walls. The coding region and exon/intron boundaries of the ANO5 gene were amplified and sequenced. The common c.191dupA mutation and a silent novel p.Leu115Leu (c.345G>A) variant were identified. This silent variant was listed neither in the LOVD database nor in the SNP database. To evaluate the pathogenicity of the novel silent mutation in ANO5, cDNA analysis was performed that demonstrated skipping of exon 6. So far, no case with a silent mutation leading to abnormal splicing has been identified in Anoctamin 5 muscular dystrophy. Present findings emphasize that cDNA analysis should be done if a silent variant is not annotated in the databases. In Anoctamin 5 muscular dystrophy a molecular diagnosis is even more important as protein investigation through Western blotting or immunohistochemistry is not yet established.
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PMID:Anoctamin 5 muscular dystrophy associated with a silent p.Leu115Leu mutation resulting in exon skipping. 2423 59