[Functional study of a gene candidate for Landouzy-Dejerine muscular dystrophy]

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) or Landouzy Dejerine muscular dystrophy affects one in 20,000 individuals. It is characterized by a progressive degeneration of skeletal muscles that progresses asymmetrically from the upper to the lower parts of the body. Although the genetic defect has been known for twelve years, the causative gene has not been identified. Patients exhibit a partial deletion in a series of repeated elements mapping close to the end of the chromosome 4 long arm. Investigators believe this deletion disturbs chromatin structure over a long distance, affecting the expression of several genes. Our laboratory has identified a gene within the repeated element itself. This gene is functional and encodes a protein, DUX4, located at the periphery of the cell nucleus. DUX4 is detected in small amounts in primary myoblasts cultures of patient but not of non-affected individuals. Its forced expression in control cells causes cell death within 48 hours. Patient primary myoblasts present oxidative stress: this phenomenon is also induced by DUX4 forced expression. In conclusion, we propose the DUX4 gene as a candidate for FSHD.