ZASP Mutation Analysis
Z-band alternatively spliced PDZ motif-containing protein gene (ZASP), also known as LIM domain-binding 3 (LDB3) and Cypher, is composed of 16 alternatively spliced exons and is located at 10q22.2-q23.3. ZASP is expressed primarily in skeletal muscle and to a lesser extent in heart and encodes four major isoforms of LIM domain-binding protein 3 by alternative splicing. LIM domain-binding protein 3 interacts with various PKC isoforms via its LIM domains and also interacts with the ACTN2 C- terminal region via its PDZ domain. It has been postulated that LIM domain-binding protein 3 may function as an adapter in striated muscle to couple protein kinase C-mediated signaling via its LIM domains to the cytoskeleton. Mutations identified in this gene cause a number of muscle-related diseases including dilated cardiomyopathy 1A (CMD1A), CMD1A with or without left ventricular non-compaction (LVNC) and ZASP-related myofibrillar myopathy (MFM). Mutations in ZASP have been noted to demonstrate autosomal dominant inheritance with a variable clinical expression. Definitive genotype/phenotype correlations have not been described.
The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for ZASP mutations. Individuals are tested by automatic fluorescent DNA sequencing of all 16 exons of the ZASP gene. 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 dilated cardiomyopathy 1A (CMD1A), CMD1A with or without left ventricular non-compaction (LVNC) and ZASP-related myofibrillar myopathy (MFM).
Genomic DNA is analyzed for ZASP mutations by automatic fluorescent DNA sequencing of all 2 exons of the ZASP 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(s) by automatic fluorescent DNA sequencing.
|Service||Direct and Institutional Billing||CPT Codes|
|Index Case (Male or Female)||$800 per sample||81406, G0452|
|Additional Family Members||$300 per sample; known familial mutation only||81403, G0452|
DNA Sequencing Analysis: Approximately 99 percent detection of mutations in exons 1-16 of ZASP.
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