Molecular genetics of charcot-marie-tooth disease: from genes to genomes.

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders of the peripheral nervous system, mainly characterized by distal muscle weakness and atrophy leading to motor handicap. With an estimated prevalence of 1 in 2,500, this condition is one of the most commonly inherited neurological disorders. Mutations in more than 30 genes affecting glial and/or neuronal functions have been associated with different forms of CMT leading to a substantial improvement in diagnostics of the disease and in the understanding of implicated pathophysiological mechanisms. However, recent data from systematic genetic screening performed in large cohorts of CMT patients indicated that molecular diagnosis could be established only in ∼50-70% of them, suggesting that additional genes are involved in this disease. In addition to providing an overview of genetic and functional data concerning various CMT forms, this review focuses on recent data generated through the use of highly parallel genetic technologies (SNP chips, sequence capture and next-generation DNA sequencing) in CMT families, and the current and future impact of these technologies on gene discovery and diagnostics of CMTs.

Functional analysis of Ectodysplasin-A mutations causing selective tooth agenesis.

Mutations of the Ectodysplasin-A (EDA) gene are generally associated with the syndrome hypohidrotic ectodermal dysplasia (MIM 305100), but they can also manifest as selective, non-syndromic tooth agenesis (MIM300606). We have performed an in vitro functional analysis of six selective tooth agenesis-causing EDA mutations (one novel and five known) that are located in the C-terminal tumor necrosis factor homology domain of the protein. Our study reveals that expression, receptor binding or signaling capability of the mutant EDA1 proteins is only impaired in contrast to syndrome-causing mutations, which we have previously shown to abolish EDA1 expression, receptor binding or signaling. Our results support a model in which the development of the human dentition, especially of anterior teeth, requires the highest level of EDA-receptor signaling, whereas other ectodermal appendages, including posterior teeth, have less stringent requirements and form normally in response to EDA mutations with reduced activity.

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, February 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, May 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, April 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, May 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, June 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, July 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, August 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, September 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, November 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, November "A" 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, December 2001

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, January 2002

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections

E-1 Monthly Statistical Movement Summary for Entire Iowa Department of Corrections, Iowa Department of Corrections, February 2002

Monthly Statistical Movement Summary for Entire Iowa Department of Corrections