Title |
Defects in fatty acid amide hydrolase 2 in a male with neurologic and psychiatric symptoms
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Published in |
Orphanet Journal of Rare Diseases, March 2015
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DOI | 10.1186/s13023-015-0248-3 |
Pubmed ID | |
Authors |
Sandra Sirrs, Clara DM van Karnebeek, Xiaoxue Peng, Casper Shyr, Maja Tarailo-Graovac, Rupasri Mandal, Daniel Testa, Devin Dubin, Gregory Carbonetti, Steven E Glynn, Bryan Sayson, Wendy P Robinson, Beomsoo Han, David Wishart, Colin J Ross, Wyeth W Wasserman, Trevor A Hurwitz, Graham Sinclair, Martin Kaczocha |
Abstract |
Fatty acid amide hydrolase 2 (FAAH2) is a hydrolase that mediates the degradation of endocannabinoids in man. Alterations in the endocannabinoid system are associated with a wide variety of neurologic and psychiatric conditions, but the phenotype and biochemical characterization of patients with genetic defects of FAAH2 activity have not previously been described. We report a male with autistic features with an onset before the age of 2 years who subsequently developed additional features including anxiety, pseudoseizures, ataxia, supranuclear gaze palsy, and isolated learning disabilities but was otherwise cognitively intact as an adult. Whole exome sequencing identified a rare missense mutation in FAAH2, hg19: g.57475100G > T (c.1372G > T) resulting in an amino acid change (p.Ala458Ser), which was Sanger confirmed as maternally inherited and absent in his healthy brother. Alterations in lipid metabolism with abnormalities of the whole blood acyl carnitine profile were found. Biochemical and molecular modeling studies confirmed that the p.Ala458Ser mutation results in partial inactivation of FAAH2. Studies in patient derived fibroblasts confirmed a defect in FAAH2 activity resulting in altered levels of endocannabinoid metabolites. We propose that genetic alterations in FAAH2 activity contribute to neurologic and psychiatric disorders in humans. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 33% |
Scientists | 1 | 33% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 1% |
Unknown | 94 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 16 | 17% |
Student > Ph. D. Student | 12 | 13% |
Researcher | 11 | 12% |
Student > Master | 11 | 12% |
Other | 7 | 7% |
Other | 17 | 18% |
Unknown | 21 | 22% |
Readers by discipline | Count | As % |
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Psychology | 20 | 21% |
Biochemistry, Genetics and Molecular Biology | 13 | 14% |
Medicine and Dentistry | 13 | 14% |
Nursing and Health Professions | 3 | 3% |
Neuroscience | 3 | 3% |
Other | 16 | 17% |
Unknown | 27 | 28% |