Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Correspondence: Norio Sakai, Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Fax: +81-6-68793939. E-mail: norio@ped.med.osaka-u.ac.jp

Received 24 November 2005; Accepted 18 February 2006; Published online 11 April 2006.

Abstract

Krabbe disease is an autosomal recessive leukodystrophy. It is pathologically characterized by demyelination of the central and peripheral nervous systems and the accumulation of globoid cells in brain white matter. It is caused by a deficiency of galactocerebrosidase (GALC) activity. We investigated mutations of the GALC gene in 17 Japanese patients with Krabbe disease, the largest subject number of Japanese patients to date, and found 27 mutations. Of these mutations, six were novel, including two nonsense mutations, W115X and R204X, two missense mutations, S257F and L364R, a small deletion, 393delT, and a small insertion, 1719-1720insT. Our findings, taken with the reported mutations in Japanese patients, confirm several mutations common to Japanese patients, the two most frequent being 12Del3Ins and I66M+I289V, which account for 37% of all mutant alleles. With two additional mutations, G270D and T652P, these account for up to 57% of genetic mutations in Japanese patients. Distribution of the mutations within the GALC gene indicated some genotype-phenotype correlation. I66M+I289M, G270D, and L618S contributed to a mild phenotype. Screening for these mutations may provide an effective method with which to predict the clinical phenotype.