Mutation of a putative protein degradation gene @entity4636 /SIMPLE in XXXX 1C.

@entity1 @entity5108 @entity72669 @entity5 @entity16 @entity128 @entity4636 @entity72668 @entity74 @entity72670
BACKGROUND: @entity5108 ( @entity5108 ) @entity16 is a heterogeneous group of @entity74 . The authors recently mapped an autosomal dominant demyelinating form of @entity5108 type 1 ( @entity72668 ) to chromosome 16p13.1-p12.3. OBJECTIVE: To find the gene mutations underlying @entity72668 . METHODS: The authors used a combination of standard positional cloning and candidate gene approaches to identify the causal gene for @entity72668 . Western blot analysis was used to determine relative protein levels in @entity1 and control lymphocyte extracts. Northern blotting was used to characterize gene expression in 1) multiple tissues; 2) developing sciatic nerve; and 3) nerve-crush and nerve-transection experiments. RESULTS: The authors identified missense mutations ( @entity72669 , @entity72670 , W116G) in the LITAFgene (lipopolysaccharide-induced @entity5 necrosis factor-alpha factor) in three @entity72668 pedigrees. @entity4636 , which is also referred to as SIMPLE, is a widely expressed gene encoding a 161-amino acid protein that may play a role in protein degradation pathways. The mutations associated with @entity72668 were found to cluster, defining a domain of the @entity4636 protein having a critical role in peripheral nerve function. Western blot analysis suggested that the @entity72670 and W116G mutations do not alter the level of @entity4636 protein in peripheral blood lymphocytes. The @entity4636 transcript is expressed in sciatic nerve, but its level of expression is not altered during development or in response to @entity128 . This finding is in stark contrast to that seen for other known genes that cause @entity72668 . CONCLUSIONS: Mutations in @entity4636 may account for a significant proportion of @entity72668 @entity1 with previously unknown molecular diagnosis and may define a new mechanism of peripheral nerve perturbation leading to demyelinating @entity16 .
