Open AccessA family with Danon disease caused by a splice site mutation in LAMP 2 that generates a truncated protein
Author(s) -
Zhou Nianwei,
Cui Jie,
Zhao Weipeng,
Jiang Yingying,
Zhu Wenqing,
Tang Lu,
Li Xuejie,
Sun Minmin,
Pan Cuizhen,
Shu Xianhong
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.561
Subject(s) - exon , lysosome , mutation , biology , autophagy , microbiology and biotechnology , genetics , gene , biochemistry , apoptosis , enzyme
Background Danon disease is an X‐linked dominant hereditary condition caused by mutations in the gene encoding lysosomal‐associated membrane protein 2 ( LAMP 2), leading to failure of lysosome binding to autophagosomes, accumulation of glycogen in the heart, and abnormal cardiac function. Methods We describe identification of a mutation in LAMP 2 , c.741+1G>T, in a family with Danon disease by whole exome sequencing. Results Pathology examination of patient skeletal muscle biopsy showed myogenic damage and autophagic vacuoles with sarcolemmal features ( AVSF ). Numerous autophagic vacuoles accumulated in muscle cells were detected by electron microscopy, indicating abnormal autophagy function. Conclusion The mutation did not result in loss of mRNA exons; rather, a 6‐nucleotide (two‐codon) insertion, where the latter was a stop codon, leading to early termination of LAMP 2 protein translation. The resulting truncated protein lacks an important transmembrane domain, which will impair lysosome/autophagosome fusion, damage autophagy function, and result in the clinical manifestations of Danon disease.