title: 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.
authors.affiliation: National Institute of Biotechnology in the Negev, Beer Sheva, Israel.
authors.forename: Miora
authors.initials: M
authors.lastname: Feinstein
authors.forename: Barak
authors.initials: B
authors.lastname: Markus
authors.forename: Iris
authors.initials: I
authors.lastname: Noyman
authors.forename: Hannah
authors.initials: H
authors.lastname: Shalev
authors.forename: Hagit
authors.initials: H
authors.lastname: Flusser
authors.forename: Ilan
authors.initials: I
authors.lastname: Shelef
authors.forename: Keren
authors.initials: K
authors.lastname: Liani-Leibson
authors.forename: Zamir
authors.initials: Z
authors.lastname: Shorer
authors.forename: Idan
authors.initials: I
authors.lastname: Cohen
authors.forename: Shareef
authors.initials: S
authors.lastname: Khateeb
authors.forename: Sara
authors.initials: S
authors.lastname: Sivan
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Birk
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D020371:Pelizaeus-Merzbacher Disease / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1