Ataxia, Dementia, and Hypogonadotropism Caused by Disordered Ubiquitination
Margolin, David H.
Lim, Elaine T.
Hall, Janet E.
Aldrin, Stephanie V.
Milunsky, Jeff M.
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CitationMargolin, David H., Maria Kousi, Yee-Ming Chan, Elaine T. Lim, Jeremy D. Schmahmann, Marios Hadjivassiliou, Janet E. Hall, et al. 2013. “Ataxia, Dementia, and Hypogonadotropism Caused by Disordered Ubiquitination.” New England Journal of Medicine 368 (21) (May 23): 1992–2003. doi:10.1056/nejmoa1215993.
AbstractIn recent years, we have seen great advances in the elucidation of genetic causes of cerebellar ataxia, with newly identified genes regulating a wide spectrum of cellular functions, including intracellular signaling, tau regulation, and mitochondrial function.1 However, a genetic defect cannot be found in approximately 40% of patients with ataxia,1 including those in whom ataxia is associated with reproductive endocrine failure, a syndrome first reported by Gordon Holmes in 1908.2 Most patients with this syndrome have a hypogonadotropic condition, with defective secretion of gonadotropins by the pituitary gland.3-12 Strikingly, genes associated with ataxia have little functional overlap with genes associated with hypogonadotropic hypogonadism, which encode proteins involved in the biologic function of the neurons that secrete gonadotropin-releasing hormone (GnRH).13
A decade ago, we described a consanguineous family with a syndrome of cerebellar ataxia, dementia, and hypogonadotropic hypogonadism.12 Here we report the results of whole-exome and targeted sequencing performed to identify mutations that underlie the syndrome in this kindred and in unrelated patients.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32697820
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