title: Farber lipogranulomatosis: clinical and molecular genetic analysis reveals a novel mutation in an Indian family.
abstract: Farber disease is a rare lysosomal storage disorder caused by a deficiency of the acid ceramidase enzyme, leading to the accumulation of ceramide in various tissues. It usually manifests within a few months after birth with a unique triad of symptoms, including painful and progressive deformed joints, progressive hoarseness and subcutaneous nodules. The disease is inherited as an autosomal recessive trait, and mutations in the N-acylsphingosine amidohydrolase (ASAH1) gene, which codes for the acid ceramidase enzyme, have been shown to cause the disease. In the current study, we report the identification of a novel disease-causing mutation in the ASAH1 gene that results in Farber disease in an Indian family. The mutation was identified in the eighth exon and is a missense mutation resulting in replacement of Valine by Leucine at codon 182. Two affected siblings harboured the identical mutation. The possible mechanism(s) of disease caused by this mutation are discussed.
authors.affiliation: Diagnostics division, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, 500076, India.
authors.forename: Akela Radha Rama
authors.initials: ARR
authors.lastname: Devi
authors.affiliation: National Genomics and Transcriptomics Facility, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, 500076, India.
authors.forename: Munimanda
authors.initials: M
authors.lastname: Gopikrishna
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, 500076, India.
authors.forename: Raman
authors.initials: R
authors.lastname: Ratheesh
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, 500076, India.
authors.forename: Gorinabele
authors.initials: G
authors.lastname: Savithri
authors.affiliation: Apollo hospitals, Hyderabad, 500003, India.
authors.forename: Gowrishankar
authors.initials: G
authors.lastname: Swarnalata
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, 500076, India. bashyam@cdfd.org.in.|National Genomics and Transcriptomics Facility, Centre for DNA Fingerprinting and Diagnostics, Nacharam, Hyderabad, 500076, India. bashyam@cdfd.org.in.
authors.forename: Murali
authors.initials: M
authors.lastname: Bashyam
mesh_terms: D055573:Acid Ceramidase; D000581:Amidohydrolases / Q000172:deficiency / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D055572:Ceramidases; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D016464:Lysosomal Storage Diseases / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid
chemical_list: D004247:DNA; D000581:Amidohydrolases; C526693:ASAH1 protein, human; D055573:Acid Ceramidase; D055572:Ceramidases