Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.

ABSTRACT:

Objective

To identify the gene responsible for 14q32-linked dominant spinal muscular atrophy with lower extremity predominance (SMA-LED, OMIM 158600).

Methods

Target exon capture and next generation sequencing was used to analyze the 73 genes in the 14q32 linkage interval in 3 SMA-LED family members. Candidate gene sequencing in additional dominant SMA families used PCR and pooled target capture methods. Patient fibroblasts were biochemically analyzed.

Results

Regional exome sequencing of all candidate genes in the 14q32 interval in the original SMA-LED family identified only one missense mutation that segregated with disease state-a mutation in the tail domain of DYNC1H1 (I584L). Sequencing of DYNC1H1 in 32 additional probands with lower extremity predominant SMA fou

SUBMITTER: Harms MB 

PROVIDER: S-EPMC3359582 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature