Expression profiling characterization of laminin α-2 positive MDC

In the Caucasian population, patients affected by the most frequent forms of congenital muscular dystrophies (MDC) are commonly divided into two groups. The first is characterized by mutations of the gene for the laminin α-2 (LAMA2). The second is positive for this protein, highly heterogeneous, and has no specific genetic defect associated yet. We studied the skeletal muscle transcriptome of four LAMA2 deficient and six LAMA2 positive MDC patients by cDNA microarrays. The expression profiling defined two patients groups: one mild and one severe phenotype. This result was in agreement with histopathological features but only partially with the clinical classification. The mild phenotype is characterized by a delayed maturation from slow to fast muscle fibers. Other muscle transcripts, such as telethonin, myosin light-chains 3 and 1 V, are underexpressed in this group. We suggest that expression profiling will provide important information to improve our understanding of the molecular basis of laminin α-2 positive MDC.