Abstract
Mutations disrupting extracellular structure of MPZ cause early onset severe forms of CMT1B
Journal of the peripheral nervous system, Vol.9(2), pp.111-112
06/2004
DOI: 10.1111/j.1085-9489.2004.009209y.x
Abstract
Missense mutations in myelin protein zero (MPZ), an important molecule for myelin compaction, cause inherited neuropathies collectively referred to as CMT1B. Depending on the mutation, phenotypes can be severe, or mild. To determine genotype-phenotype correlations in CMT1B we evaluated patients from 11 different families seen in our clinic and 80 reported cases from the literature with respect to (1) how the mutation affected amino acids known to be critical for homotypic MPZ interactions; (2) whether the mutation affected the charge or hydrophobicity of an amino acid; (3) whether the mutation was likely to affect the secondary or tertiary structure of the MPZ, or (4) whether it affected evolutionarily conserved amino acids. We found that mutations that added a charged residue to the extracellular domain, introduced a cysteine or altered a conserved amino acid, caused a severe neuropathy. Mutation of an amino acid critical for cis or trans homotypic adhesion, however, had no obvious consequences on disease severity. We conclude that mutations which significantly disrupt the secondary or tertiary structure of MPZ are likely to cause severe, early onset neuropathies, whereas mutations which do not cause milder disease. Studies on how mutations disrupt protein trafficking and adhesion are underway.
Details
- Title: Subtitle
- Mutations disrupting extracellular structure of MPZ cause early onset severe forms of CMT1B
- Creators
- M Grandis - Università di Genova, Genova, ItalyM Jain - Wayne State University, Detroit MI, USAV La Padula - Università di Genova, Genova, ItalyJ Balsamo - University of Iowa, Iowa City, IA, USAJ Lilien - University of Iowa, Iowa City, IA, USAJ Kamholz - Wayne State University, Detroit MI, USAA Schenone - Università di Genova, Genova, ItalyM E Shy - Università di Genova, Genova, Italy
- Resource Type
- Abstract
- Publication Details
- Journal of the peripheral nervous system, Vol.9(2), pp.111-112
- Publisher
- Blackwell Science Inc; Oxford, UK; Malden, USA
- DOI
- 10.1111/j.1085-9489.2004.009209y.x
- ISSN
- 1085-9489
- eISSN
- 1529-8027
- Number of pages
- 2
- Language
- English
- Date published
- 06/2004
- Academic Unit
- Iowa Neuroscience Institute; Stead Family Department of Pediatrics; Molecular Physiology and Biophysics; Biology; Psychiatry; Internal Medicine; Neurology
- Record Identifier
- 9984072070902771
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