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Human acid ceramidase gene: novel mutations in Farber disease
- Source :
- Molecular genetics and metabolism. 70(4)
- Publication Year :
- 2000
-
Abstract
- Farber disease is an autosomal recessive disorder caused by lysosomal acid ceramidase (AC) deficiency. It commonly manifests during the first few months after birth with a unique triad of painful and progressive deformed joints, subcutaneous nodules, and progressive hoarseness. In order to understand the molecular mechanism(s) of pathogenesis of Farber disease, we isolated and characterized a full-length human AC gene, mapped its chromosomal location, determined the tissue-specific expression, and analyzed mutations in Farber disease patients. We also studied the AC-mRNA expression in gastrointestinal tumors and adjoining normal tissues. In addition, we determined the pattern of tissue-specific AC-mRNA expression in the adult mouse and during fetal development. Our results show that human AC gene consists of 14 exons and 13 introns spanning approximately 26.5 kb of genomic DNA. It is mapped to human chromosome 8p22–21.2, a region often disrupted in several cancers. The AC-mRNA is expressed in the mouse fetus from the seventh day of gestation. Interestingly, while the AC-mRNA is expressed in all segments of the normal gastrointestinal tract, none of the gastrointestinal tumor tissues had any AC-mRNA expression. We also uncovered four novel mutations in Farber disease patients that were not previously reported. Taken together, our results not only attest to the physiological importance of AC but also uncover several new mutations in Farber disease that may advance our knowledge towards establishing a genotype–phenotype correlation in this disease.
- Subjects :
- Acid Ceramidase
Endocrinology, Diabetes and Metabolism
Gene mutation
Biology
Biochemistry
Amidohydrolases
Pathogenesis
Exon
Embryonic and Fetal Development
Mice
Endocrinology
Genetics
medicine
Ceramidases
Animals
Humans
RNA, Messenger
Molecular Biology
Gene
Cells, Cultured
In Situ Hybridization, Fluorescence
DNA Primers
Gastrointestinal tract
Farber disease
Base Sequence
Chromosome Mapping
medicine.disease
Molecular biology
Lysosomal Storage Diseases
genomic DNA
Mutation
Subjects
Details
- ISSN :
- 10967192
- Volume :
- 70
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Molecular genetics and metabolism
- Accession number :
- edsair.doi.dedup.....5a5b12cae25700b9322b2e701f24d626