Is there evidence for neuropsychological and neurobehavioral phenotypes among adults without FXTAS who carry the FMR1 premutation? A review of current literature

• Type of Material: Article
• Authors: Jessica Ezzell Hunter, Emory University; Ann Abramowitz, Emory University; Michele Rusin, Independent Practice, Georgia; Stephanie Sherman, Emory University
• Language: English
• Date: 2009-02
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Lippincott Williams & Wilkins
• Final Published Version (URL): http://www.nature.com/gim/journal/v11/n2/full/gim200910a.html
• Title of Journal or Parent Work: Genetics in Medicine
• ISSN: 1098-3600
• Volume: 11
• Issue: 2
• Start Page: 79
• End Page: 89
• Grant/Funding Information: This work was supported by NIH R01 HD29909 and P30 HD24064.
• Keywords: FXTAS; fragile × syndrome; CGG repeat; premutation; cognition; depression; neuropsychology; FMR1; anxiety
• Research Categories: Psychology, Behavioral; Biology, Genetics; Health Sciences, General

Abstract

Carriers of expanded, but unmethylated, premutation alleles of the fragile × mental retardation gene (FMR1) are at risk for a late-onset tremor/ataxia syndrome, mostly affecting men over age 50. However, the general neuropsychological and neurobehavioral impact of carrying a premutation allele in younger adults not affected by the tremor/ataxia syndrome remains unclear. Past studies have utilized varying study designs resulting in inconsistent conclusions. To better understand the current evidence of the influence of the premutation on such traits in adult carriers, we reviewed the literature and identified 16 studies that met conservative inclusion criteria, including molecular measures of the FMR1 CGG triplet repeat length and standard measures of neurobehavioral and neurocognitive phenotypes. A review of these studies is presented to assess the evidence for possible premutation-associated neuropsychological deficits among adult men and women who do not meet diagnostic criteria of the tremor/ataxia syndrome. Results of these studies, as well as possible reasons for inconsistent conclusions, are discussed. The primary conclusion from this review is the need for further research using a standard protocol in a large multi-site project to ensure the necessary sample size.