LAMP2 Mutation Analysis
LAMP-2 is a lysosomal protein that coats the inner surface of the lysosomal membrane. Although the functions of LAMP-2 remain unclear, roles in cell-cell or cell-extracellular matrix adhesion and as a receptor for substrates of chaperone-mediated autophagy have been proposed. LAMP-2 is encoded by the LAMP2 gene composed of ten exons and located at Xq24. Alternative splicing of the LAMP2 mRNA results in two isoforms with differential expression patterns.
Mutations in the LAMP2 gene have been shown to cause Danon disease, which is a lysosomal glycogen storage disease characterized clinically by cardiomyopathy (hypertrophic or dilated), skeletal myopathy and variable mental retardation, with intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Other manifestations of Danon disease can include Wolff-Parkinson White syndrome, increased serum creatine kinase and ophthalmic abnormalities. Danon disease demonstrates an X-linked dominant pattern of inheritance with incomplete penetrance and most often a milder phenotype in females.
Mutations in LAMP2 can also cause hypertrophic or dilated cardiomyopathy with skeletal myopathy and/or WPW. Female carriers manifest cardiomyopathy during adulthood, while affected males usually develop symptoms before the age of 20 years. Female carriers also have skeletal myopathy and mental retardation less commonly than do affected males.
The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for LAMP2 mutations. Individuals are tested by automatic fluorescent DNA sequencing of all ten exons of the LAMP2 gene. We strongly recommend initial testing of an affected individual, if available, in order to provide the greatest test sensitivity and clearest interpretation of results for subsequent family members. Genetic counseling is recommended for all individuals in order to identify additional at-risk family members and to discuss reproductive issues.
Reasons for Referral
- Molecular confirmation of the diagnosis of Danon disease, or hypertrophic or dilated cardiomyopathy with skeletal myopathy and/or Wolff-Parkinson White syndrome in affected males and females
- Carrier testing in asymptomatic females with a family history of Danon disease, or hypertrophic or dilated cardiomyopathy with skeletal myopathy and/or Wolff-Parkinson White syndrome
Genomic DNA is analyzed for LAMP2 mutations by automatic fluorescent DNA sequencing of all ten exons of the LAMP2 gene, as well as the exon/intron junctions and a portion of the 5′ and 3′ untranslated regions. Patient DNA is sequenced in both the forward and reverse orientations. If a mutation is identified, additional family members are analyzed only for the familial mutation by automatic fluorescent DNA sequencing.
|Service||Direct and Institutional Billing||CPT Codes|
|Index Case (Male or Female)||$750 per sample||81405, G0452|
|Additional Family Members||$300 per sample; known familial mutation only||81403, G0452|
DNA Sequencing Analysis: Approximately 99 percent detection of mutations in exons 1-10 of LAMP2.
Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek