Danon disease: further clinical and molecular heterogeneity.
Two families of Greek patients with subclinical to severe cardiomyopathy are presented. The diagnosis of Danon disease was supported by a total lack of LAMP2 immunostaining in cultured skin fibroblasts and muscle biopsies. The LAMP2 mutation carried by one patient (c.928G>A) has already been reported but with different symptoms. The second patient had a novel point deletion. This has not been described previously, but it could be detected easily by restriction analysis. This mutation was also found in the patient's brother, and it was associated with severe cardiomyopathy leading to heart failure. Surprisingly, the proband also had partial reduction of alpha-galactosidase A activity, despite the absence of characteristic clinical features of Fabry disease. A substitution in the GLA gene (c.937G>T) was found, and its involvement in the cardiac disease is discussed.
Sabourdy
Frédérique
F
Laboratoire de Biochimie "Maladies Métaboliques," Institut Fédératif de Biologie, CHU Purpan, Toulouse, France.
Michelakakis
Helen
H
Anastasakis
Aris
A
Garcia
Virginie
V
Mavridou
Irene
I
Nieto
Michèle
M
Pons
Marie-Claude
MC
Skiadas
Constantinos
C
Moraitou
Marina
M
Manta
Panagiota
P
Elleder
Milan
M
Levade
Thierry
T
D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D052120:Glycogen Storage Disease Type IIb / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007438:Introns / Q000235:genetics; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D000519:alpha-Galactosidase / Q000235:genetics
D005819:Genetic Markers; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D000519:alpha-Galactosidase