Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease

T. Muramatsu, N. Sakai, I. Yanagihara, M. Yamada, T. Nishigaki, C. Kokubu, H. Tsukamoto, Makoto Ito, K. Inui

Research output: Contribution to journalReview article

15 Citations (Scopus)

Abstract

Farber disease is a rare lysosomal storage disease, characterized by the accumulation of ceramide in tissues due to acid ceramidase deficiency. Here we report the identification of three novel mutations in the acid ceramidase gene from two Japanese patients. Patient 1 showed joint problems at around 10 months of age and the patient is now emaciated, with multiple nodules and mild neurological problems at 10 years of age. Patient 2 had consanguineous parents and showed joint contractures at around 8 months of age. He showed neurological symptoms around 2 years of age and died at 6 years owing to respiratory failure. The diagnosis was made clinically and was confirmed by enzymatic assay of acid ceramidase. Molecular analysis of cultured skin fibroblasts showed normal mRNA levels expressed in both patients. By direct sequencing of cDNA, missense mutations of V97E in exon 4 and G235R in exon 9 were detected in patient 1 and 96delV in exon 4 was homozygously identified in patient 2. These mutations were also confirmed in genomic DNA. Expression of mutated acid ceramidase cDNA in COS-1 cells showed acid ceramidase activity decreased to 35%, 2% and 37% of control value, respectively. We also found a new polymorphism V369I in exon 14 in the allele from the mother of patient 1. To date, 13 mutations, including our newly identified mutations, have been reported. All these mutations were genetically private and genotype-phenotype correlations could not be made.

Original languageEnglish
Pages (from-to)585-592
Number of pages8
JournalJournal of Inherited Metabolic Disease
Volume25
Issue number7
DOIs
Publication statusPublished - Nov 1 2002

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Farber Lipogranulomatosis
Acid Ceramidase
Mutation
Genes
Exons
Complementary DNA
Joints
Lysosomal Storage Diseases
Ceramides
COS Cells
Enzyme Assays
Genetic Association Studies
Contracture
Missense Mutation
Respiratory Insufficiency
Fibroblasts
Parents
Alleles
Mothers

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Muramatsu, T., Sakai, N., Yanagihara, I., Yamada, M., Nishigaki, T., Kokubu, C., ... Inui, K. (2002). Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease. Journal of Inherited Metabolic Disease, 25(7), 585-592. https://doi.org/10.1023/A:1022047408477

Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease. / Muramatsu, T.; Sakai, N.; Yanagihara, I.; Yamada, M.; Nishigaki, T.; Kokubu, C.; Tsukamoto, H.; Ito, Makoto; Inui, K.

In: Journal of Inherited Metabolic Disease, Vol. 25, No. 7, 01.11.2002, p. 585-592.

Research output: Contribution to journalReview article

Muramatsu, T, Sakai, N, Yanagihara, I, Yamada, M, Nishigaki, T, Kokubu, C, Tsukamoto, H, Ito, M & Inui, K 2002, 'Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease', Journal of Inherited Metabolic Disease, vol. 25, no. 7, pp. 585-592. https://doi.org/10.1023/A:1022047408477
Muramatsu, T. ; Sakai, N. ; Yanagihara, I. ; Yamada, M. ; Nishigaki, T. ; Kokubu, C. ; Tsukamoto, H. ; Ito, Makoto ; Inui, K. / Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease. In: Journal of Inherited Metabolic Disease. 2002 ; Vol. 25, No. 7. pp. 585-592.
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