081 Analysis of TAZ (tafazzin) and LDB3 (LIM domain-binding3/Cypher/ZASP) genes in Left ventricular non compaction

Abstract

Left ventricular non compaction (LVNC) is a recently identified cardiomyopathy, characterized by an excessively prominent trabecular meshwork and deep intertrabecular recesses. Some genes have been described as responsible for LVNC, including TAZ and LDB3, but the precise prevalence of these genes and the impact of mutation screening in clinical practice are poorly understood. To assess the prevalence of mutations in TAZ (tafazzin, Xq28) and LDB3 (LIM domain-binding3/Cypher/ZASP, 10q23.2) genes in a large cohort of patients with LVNC, whatever the familial context. DNA was extracted from a population of 59 consecutive patients with a definitive diagnosis of LVNC (Echo core lab), from the French registry of LVNC. Direct sequencing of exons and intron-exon boundaries was performed with ABI Prism 3100 Genetic Analyzer (Applied Biosystems). The suspected mutations were tested in a control population (>240 chromosomes); segregation within the families were analysed when available; evolutive conservation among various species were analysed by multiple alignement. We identified two new missense mutations in the TAZ gene (Phe128Ser and Met155Val) in two index male patients. No mutation was observed in the LDB3 gene, but two new genetic polymorphisms. The prevalence of TAZ mutations was 3% (2/59) and 0% for LDB3. Mutations in TAZ gene were not unfrequent in LVNC whereas no mutation was observed in LDB3 gene. These findings may have impact for LVNC mutation screening strategy in clinical practice, and also for genetic counselling as TAZ mutations are associated with X-linked inheritance.