title: Pathological Effects of the FMR1 CGG-Repeat Polymorphism (5-55 Repeat Numbers): Systematic Review and Meta-Analysis.
abstract: The fragile X mental retardation 1 (FMR1) gene contains a highly polymorphic trinucleotide (CGG) repeat and consists of various allelic forms. Traditionally, 55-200 repeats and over 200 CGG repeats have been highlighted to be associated with ovarian dysfunction and neuro-psychiatric risks. However, previous studies had paid little attention to the allelic forms of 5-55 CGG repeats. Herein, we sought to evaluate the pathological features of FMR1 allelic category with a range of 5-55 CGG repeats. We further classified the spectrum of CGG sizes (5-55 repeats) into three sub-groups as low numbers of CGG repeat (< 26 repeats), normal CGG count (26-34 repeats), and small CGG expansion (35-54 repeats). Our systematic review documented that low numbers of CGG repeat (< 26 repeats) revealed a close relationship with premature ovarian failure. Correspondingly, the meta-analysis showed that small CGG expansion, involving allelic sizes with 35-54 (n = 8, OR = 1.22, 95% CI: 0.75-2.00, P > 0.05) and 41-54 (n = 7, OR = 1.62, 95% CI: 1.14-2.30, P < 0.05), was both linked to the risk of ovarian dysfunction. Additionally, small CGG expansion exerts significant influence on male Parkinsonism cohorts (OR = 2.17, 95% CI: 1.50-3.14, P < 0.05), mental retardation, and repeat instability. Our data provide evidence that the CGG-repeat numbers below 26 or above 34 of FMR1 gene are also associated with disease risks and thus should be regarded as pathological genotypes for a routine test.
authors.affiliation: Department of Clinical Genetics and Experimental Medicine, Affiliated Dongfang Hospital of Xiamen University.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yang
authors.forename: Cuihua
authors.initials: C
authors.lastname: Fan
authors.forename: Liangyuan
authors.initials: L
authors.lastname: Chen
authors.forename: Zhaolei
authors.initials: Z
authors.lastname: Cui
authors.forename: Ye
authors.initials: Y
authors.lastname: Bai
authors.forename: Fenghua
authors.initials: F
authors.lastname: Lan
mesh_terms: D056915:DNA Copy Number Variations; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497683:FMR1 protein, human