title: Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration.
abstract: Fatty acid hydroxylase-associated neurodegeneration due to fatty acid 2-hydroxylase deficiency presents with a wide range of phenotypes including spastic paraplegia, leukodystrophy, and/or brain iron deposition. All previously described families with this disorder were consanguineous, with homozygous mutations in the probands. We describe a 10-year-old male, from a non-consanguineous family, with progressive spastic paraplegia, dystonia, ataxia, and cognitive decline associated with a sural axonal neuropathy. The use of high-throughput sequencing techniques combined with SNP array analyses revealed a novel paternally derived missense mutation and an overlapping novel maternally derived ~28-kb genomic deletion in FA2H. This patient provides further insight into the consistent features of this disorder and expands our understanding of its phenotypic presentation. The presence of a sural nerve axonal neuropathy had not been previously associated with this disorder and so may extend the phenotype.
authors.affiliation: NIH Undiagnosed Diseases Program, NIH Office of Rare Diseases Research and NHGRI, Bethesda, 35 Convent Drive, Bethesda, MD 20892, USA.piersonty@ninds.nih.gov
authors.forename: Tyler Mark
authors.initials: TM
authors.lastname: Pierson
authors.forename: Dimitre R
authors.initials: DR
authors.lastname: Simeonov
authors.forename: Murat
authors.initials: M
authors.lastname: Sincan
authors.forename: David A
authors.initials: DA
authors.lastname: Adams
authors.forename: Thomas
authors.initials: T
authors.lastname: Markello
authors.forename: Gretchen
authors.initials: G
authors.lastname: Golas
authors.forename: Karin
authors.initials: K
authors.lastname: Fuentes-Fajardo
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Hansen
authors.forename: Praveen F
authors.initials: PF
authors.lastname: Cherukuri
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.forename: Craig
authors.initials: C
authors.lastname: Blackstone
authors.forename: Cynthia
authors.initials: C
authors.lastname: Tifft
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D056915:DNA Copy Number Variations; D059472:Exome / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D006899:Mixed Function Oxygenases; C019081:fatty acid alpha-hydroxylase