Pelizaeus-merzbacher-like disease caused by AIMP1/p43 homozygous mutation

Miora Feinstein, Barak Markus, Iris Noyman, Hannah Shalev, Hagit Flusser, Ilan Shelef, Keren Liani-Leibson, Zamir Shorer, Idan Cohen, Shareef Khateeb, Sara Sivan, Ohad S. Birk

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


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.

Original languageEnglish
Pages (from-to)820-828
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number6
StatePublished - 10 Dec 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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