title: Molecular analyses of novel ASAH1 mutations causing Farber lipogranulomatosis: analyses of exonic splicing enhancer inactivating mutation.
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.
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
authors.forename: M D
authors.initials: MD
authors.lastname: Bashyam
authors.forename: A K
authors.initials: AK
authors.lastname: Chaudhary
authors.forename: M
authors.initials: M
authors.lastname: Kiran
authors.forename: V
authors.initials: V
authors.lastname: Reddy
authors.forename: H A
authors.initials: HA
authors.lastname: Nagarajaram
authors.forename: A
authors.initials: A
authors.lastname: Dalal
authors.forename: L
authors.initials: L
authors.lastname: Bashyam
authors.forename: D
authors.initials: D
authors.lastname: Suri
authors.forename: A
authors.initials: A
authors.lastname: Gupta
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: M
authors.initials: M
authors.lastname: Kabra
authors.forename: R D
authors.initials: RD
authors.lastname: Puri
authors.forename: R
authors.initials: R
authors.lastname: RamaDevi
authors.forename: S
authors.initials: S
authors.lastname: Kapoor
authors.forename: S
authors.initials: S
authors.lastname: Danda
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics*; D002675:Child, Preschool; D005091:Exons; D055577:Farber Lipogranulomatosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D012326:RNA Splicing
chemical_list: C526693:ASAH1 protein, human; D055573:Acid Ceramidase
keywords: 5′ splice site; ASAH1; Farber disease; acid ceramidase; exon skipping; exonic splicing enhancer; polypyrimidine tract