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Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis: analyses of exonic splicing enhancer inactivating mutation |
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| Authors: | M.D. Bashyam A.K. Chaudhary M. Kiran V. Reddy H.A. Nagarajaram A. Dalal L. Bashyam D. Suri A. Gupta N. Gupta M. Kabra R.D. Puri R. RamaDevi S. Kapoor S. Danda |
| Affiliation: | 1. Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, , Hyderabad, India;2. Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics, , Hyderabad, India;3. Diagnostics Division, Centre for DNA Fingerprinting and Diagnostics, , Hyderabad, India;4. School of Life Sciences, University of Hyderabad, , Hyderabad, India;5. Department of Pediatrics, Post Graduate Institute of Medical Education and Research, , Chandigarh, India;6. Department of Pediatrics, All India Institute of Medical Sciences, , New Delhi, India;7. Deparment of Genetic Medicine, Sir Ganga Ram Hospital, , Delhi, India;8. Sandor Proteomics, , Hyderabad, India;9. Division of Genetics, Lok Nayak Hospital & Maulana Azad Medical College, , New Delhi, India;10. Department of Clinical Genetics, Christian Medical College and Hospital, , Vellore, India |
| Abstract: | Farber lipogranulomatosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the ASAH1 gene. In the largest ever study, we identified and characterized ASAH1 mutations from 11 independent Farber disease (FD) families. A total of 13 different mutations were identified including 1 splice, 1 polypyrimidine tract (PPT) deletion and 11 missense mutations. Eleven mutations were exclusive to the Indian population. The IVS6+4A>G splice and IVS5‐16delTTTTC PPT deletion mutations resulted in skipping of exon 6 precluding thereby the region responsible for cleavage of enzyme precursor. A missense mutation (p.V198A) resulted in skipping of exon 8 due to inactivation of an exonic splicing enhancer (ESE) element. This is the first report of mutations affecting PPT and ESE in the ASAH1 gene resulting in FD. |
| Keywords: | 5′ splice site acid ceramidase ASAH1 exon skipping exonic splicing enhancer Farber disease polypyrimidine tract |