The Frequency of c.550delA Mutation of the CANP3 Gene in the Polish LGMD2A Population.
BACKGROUND
Limb girdle muscular dystrophy 2A (LGMD2A) is the most frequent LGMD variant in the European population, representing about 40% of LGMD. The c.550delA mutation in the CANP3 (calcium activated neutral protease 3) gene is the most commonly reported mutation in LGMD2A. Prevalence of this mutation in the Polish population has not been previously investigated. The aim of this study was to identify and estimate the frequency of the c.550delA mutation in Polish LGMD2A patients.


METHODS
Polymerase chain reaction-sequencing analysis, restriction fragment length polymorphism polymerase chain reaction method.


RESULTS
We analyzed 76 families affected with LGMD and identified 62 probands with mutations in the CANP3 gene. C.550delA was the most common mutation identified, being found in 78% of the LGMD2A families. The remaining mutations observed multiple times were as follows: c.598-612del15ntd; c.2242C>T; c.418dupC; c.1356insT, listed in terms of decreasing frequency. Two novel variants in the CANP3 gene, that is, c.700G>A Gly234Arg and c.661G>A Gly221Ser were also characterized. Overall, mutations in the LGMD2A gene were estimated to be present in 81% of patients with the LGMD phenotype who were without sarcoglycans and dysferlin deficiency on immunocytochemical analysis. The frequency of the heterozygous c.550delA mutation in the healthy Polish population was estimated at 1/124.


CONCLUSIONS
The c.550delA is the most frequent CANP3 mutation in the Polish population, thus sequencing of exon 4 of this gene could identify the majority of LGMD2A patients in Poland.
1 Department of Neurology, Central Clinical Hospital of the Ministry of Interior in Warsaw , Warsaw, Poland .
Małgorzata
M
Dorobek
2 Department of Neurology, Warsaw Medical University , Poland .
Barbara
B
Ryniewicz
3 Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland .
Dagmara
D
Kabzińska
3 Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland .
Anna
A
Fidziańska
1 Department of Neurology, Central Clinical Hospital of the Ministry of Interior in Warsaw , Warsaw, Poland .|4 Department of Neurodegenerative Disorders, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland .
Maria
M
Styczyńska
3 Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences , Warsaw, Poland .
Irena
I
Hausmanowa-Petrusewicz
D002154:Calpain / Q000235:genetics*; D000073939:Dysferlin; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011044:Poland / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D015995:Prevalence; D049031:Sarcoglycans / Q000378:metabolism
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D049031:Sarcoglycans; C105884:CAPN3 protein, human; D002154:Calpain