Entire CAPN3 gene deletion in a patient with limb-girdle muscular dystrophy type 2A.
Limb-girdle muscular dystrophy type 2A (LGMD2A) due to mutations in the CAPN3 gene is one of the most common of autosomal recessive limb-girdle muscular dystrophies. We describe a patient who had a typical LGMD2A phenotype and posterior compartment involvement on MRI. Different genetic analyses were performed, including microarray analysis. There was an apparently homozygous mutation in exon 24, c.2465G>T, p.(*822Leuext62*), and a lack of correlation in the disease segregation analyses. This suggested the presence of a genomic rearrangement. In fact, a heterozygous deletion of the entire CAPN3 gene was found. This novel deletion comprised the terminal region of the GANC gene and the entire CAPN3 gene. This finding points out the need to reconsider and adapt our current strategy of molecular diagnosis in order to detect these types of genomic rearrangements that escape standard mutation screening procedures.
Neurosciences Area, Biodonostia Institute, Hospital Universitario Donostia, 20014, San Sebastián, Spain.
Oihane
O
Jaka
Margarita
M
Azpitarte
Coro
C
Paisán-Ruiz
Miren
M
Zulaika
Leire
L
Casas-Fraile
Raúl
R
Sanz
Nathalie
N
Trevisiol
Nicolas
N
Levy
Marc
M
Bartoli
Martin
M
Krahn
Adolfo
A
López de Munain
Amets
A
Sáenz
D002154:Calpain / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D008279:Magnetic Resonance Imaging; D046228:Microarray Analysis; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
D018076:DNA, Complementary; D009124:Muscle Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; C105884:CAPN3 protein, human; D002154:Calpain
CAPN3; deletion; genomic rearrangement; homozygous mutation; limb-girdle muscular dystrophy type 2A