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Am J Hum Genet. 2010 Dec 10;87(6):820-8. doi: 10.1016/j.ajhg.2010.10.016. Epub 2010 Nov 18.

Pelizaeus-Merzbacher-like disease caused by AIMP1/p43 homozygous mutation.

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  • 1National Institute of Biotechnology in the Negev, Beer Sheva, Israel.

Abstract

Pelizaeus-Merzbacher disease is an X-linked hypomyelinating leukodystrophy caused by PLP1 mutations. A similar autosomal-recessive phenotype, Pelizaeus-Merzbacher-like disease (PMLD), has been shown to be caused by homozygous mutations in GJC2 or HSPD1. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD in which linkage to PLP1, GJC2, and HSPD1 was excluded. Through genome-wide homozygosity mapping and mutation analysis, we demonstrated in all affected individuals a homozygous frameshift mutation that fully abrogates the main active domain of AIMP1, encoding ARS-interacting multifunctional protein 1. The mutation fully segregates with the disease-associated phenotype and was not found in 250 Bedouin controls. Our findings are in line with the previously demonstrated inability of mutant mice lacking the AIMP1/p43 ortholog to maintain axon integrity in the central and peripheral neural system.

Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Comment in

  • Neurodegenerative disorder related to AIMP1/p43 mutation is not a PMLD. [Am J Hum Genet. 2011]
  • AIMP1/p43 mutation and PMLD. [Am J Hum Genet. 2011]
PMID:
21092922
[PubMed - indexed for MEDLINE]
PMCID:
PMC2997381
Free PMC Article

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