Congenital lethal motor neuron disease with a novel defect in ribosome biogenesis.

ABSTRACT:

Objective

We describe a novel congenital motor neuron disease with early demise due to respiratory insufficiency with clinical overlap with spinal muscular atrophy with respiratory distress (SMARD) type 1 but lacking a mutation in the IGHMBP2 gene.

Methods

Exome sequencing was used to identify a de novo mutation in the LAS1L gene in the proband. Pathogenicity of the mutation was validated using a zebrafish model by morpholino-mediated knockdown of las1l.

Results

We identified a de novo mutation in the X-linked LAS1L gene in the proband (p.S477N). The mutation is in a highly conserved region of the LAS1L gene predicted to be deleterious by bioinformatic analysis. Morpholino-based knockdown of las1l, the orthologous gene in zebrafish, results in early lethality and disr

SUBMITTER: Butterfield RJ 

PROVIDER: S-EPMC4001186 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature