Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration

Tyler Mark Pierson, Dimitre R. Simeonov, Murat Sincan, David A. Adams, Thomas Markello, Gretchen Golas, Karin Fuentes-Fajardo, Nancy F. Hansen, Praveen F. Cherukuri, Pedro Cruz, James C. Mullikin, Craig Blackstone, Cynthia Tifft, Cornelius F. Boerkoel, William A. Gahl

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)476-479
Number of pages4
JournalEuropean Journal of Human Genetics
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2012

Fingerprint

Exome
Paraplegia
Single Nucleotide Polymorphism
Phenotype
Sural Nerve
Dystonia
Missense Mutation
Ataxia
Mixed Function Oxygenases
Fatty Acids
Iron
Mutation
Brain
Fatty Acid Hydroxylase-Associated Neurodegeneration
Cognitive Dysfunction
sural

Keywords

  • deletion analysis
  • exome sequencing
  • fatty acid 2-hydroxylase
  • fatty acid hydroxylase-associated neurodegeneration
  • neuropathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. / Pierson, Tyler Mark; Simeonov, Dimitre R.; Sincan, Murat; Adams, David A.; Markello, Thomas; Golas, Gretchen; Fuentes-Fajardo, Karin; Hansen, Nancy F.; Cherukuri, Praveen F.; Cruz, Pedro; Mullikin, James C.; Blackstone, Craig; Tifft, Cynthia; Boerkoel, Cornelius F.; Gahl, William A.

In: European Journal of Human Genetics, Vol. 20, No. 4, 01.04.2012, p. 476-479.

Research output: Contribution to journalArticle

Pierson, TM, Simeonov, DR, Sincan, M, Adams, DA, Markello, T, Golas, G, Fuentes-Fajardo, K, Hansen, NF, Cherukuri, PF, Cruz, P, Mullikin, JC, Blackstone, C, Tifft, C, Boerkoel, CF & Gahl, WA 2012, 'Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration', European Journal of Human Genetics, vol. 20, no. 4, pp. 476-479. https://doi.org/10.1038/ejhg.2011.222
Pierson, Tyler Mark ; Simeonov, Dimitre R. ; Sincan, Murat ; Adams, David A. ; Markello, Thomas ; Golas, Gretchen ; Fuentes-Fajardo, Karin ; Hansen, Nancy F. ; Cherukuri, Praveen F. ; Cruz, Pedro ; Mullikin, James C. ; Blackstone, Craig ; Tifft, Cynthia ; Boerkoel, Cornelius F. ; Gahl, William A. / Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration. In: European Journal of Human Genetics. 2012 ; Vol. 20, No. 4. pp. 476-479.
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