Danon disease diagnosis by targeted next-generation sequencing: identification of LAMP2 mutations
The case report of the Danon disease firstly diagnosed in Belarus is presented. The targeted Next-Generation Sequencing (tNGS) was used to search for mutations in 46 genes associated with cardiomyopathy of different genesis in a patient suffered from dilated cardiomyopathy, peripheral muscle disorders and mild dementia. Hemizygous deletion c.864+3_864+6delGAGT (rs397516751, NM_002294.2) in the LAMP2 gene affecting the natural splice site was detected. The LAMP2 gene (Lysosomal Associated Membrane Protein 2, Xq24) encodes a membrane glycoprotein essential for the adhesion of lysosomes. Mutations in LAMP2 lead to the distortion of the autophagy by lysosomes and glycogen accumulation in the cells. Clinically, they manifest in the Danon disease: hypertrophic or dilated cardiomyopathy, skeletal myopathy, and mental retardation. The metabolic reason of cardiomyopathy has not been recognized in the present case. The tNGS has allowed one to correct the diagnosis. The early exact diagnosis for such patients is essential to slow down the disease progression. The Danon disease can proceed asymptomatically before puberty and then develops rapidly with sudden mortality.