Anoctamin 5 muscular dystrophy associated with a silent p.Leu115Leu mutation resulting in exon skipping.
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.
Department of Neurology, Martin-Luther-University Halle-Wittenberg, Germany. Electronic address: pushpa.joshi@medizin.uni-halle.de.
Pushpa Raj
PR
Joshi
Genetikum, Neu-Ulm, Germany.
Dieter
D
Gläser
Genetikum, Neu-Ulm, Germany.
Carolin
C
Dreßel
Institute of Human Genetics, Biozentrum, University Würzburg, Germany.
Wolfram
W
Kress
Institute of Neuropathology, RWTH Aachen, Germany.
Joachim
J
Weis
Department of Neurology, Martin-Luther-University Halle-Wittenberg, Germany.
Marcus
M
Deschauer
D000075368:Anoctamins; D018118:Chloride Channels / Q000235:genetics*; D005091:Exons; D006801:Humans; D008297:Male; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation
C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels
Anoctamin 5; Dysferlin; Exon skipping; Mutation; Silent mutation