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


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.

SUBMITTER: Feinstein M 

PROVIDER: S-EPMC2997381 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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

Feinstein Miora M   Markus Barak B   Noyman Iris I   Shalev Hannah H   Flusser Hagit H   Shelef Ilan I   Liani-Leibson Keren K   Shorer Zamir Z   Cohen Idan I   Khateeb Shareef S   Sivan Sara S   Birk Ohad S OS  

American journal of human genetics 20101118 6


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 demonstrate  ...[more]

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