Pelizaeus-Merzbacher-like Disease Caused by AIMP1/p43 Homozygous Mutation

作者：Feinstein Miora; Markus Barak; Noyman Iris; Shalev Hannah; Flusser Hagit; Shelef Ilan; Liani Leibson Keren; Shorer Zamir; Cohen Idan; Khateeb Shareef; Sivan Sara; Birk Ohad S^*

来源：American Journal of Human Genetics, 2010, 87(6): 820-828.

DOI：10.1016/j.ajhg.2010.10.016

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.

• 出版日期2010-12-10