Tohoku J. Exp. Med., 2016 May, 239(1)

Review

Pathological Effects of the FMR1 CGG-Repeat Polymorphism (5-55 Repeat Numbers): Systematic Review and Meta-Analysis

WENJING YANG,1 CUIHUA FAN,2 LIANGYUAN CHEN,2 ZHAOLEI CUI,2 YE BAI3 and FENGHUA LAN1

1Department of Clinical Genetics and Experimental Medicine, Affiliated Dongfang Hospital of Xiamen University, Fuzhou, Fujian, P.R. China
2Department of Clinical Genetics and Experimental Medicine, Fujian Medical University, Fuzhou, Fujian, P.R. China
3Department of Clinical Genetics and Experimental Medicine, Fuzhou General Hospital, Fuzhou, Fujian, P.R. China

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.

Key words —— disease risks; low numbers of CGG repeat; meta-analysis; ovarian dysfunction; small CGG expansion

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Tohoku J. Exp. Med., 2016, 239, 57-66

Correspondence: Fenghua Lan, Department of Clinical Genetics and Experimental Medicine, Affiliated Dongfang Hospital of Xiamen University, No.156, Xier Huan Road, Gulou District, Fuzhou, Fujian 350025, P.R. China.

e-mail: xmulfh@sina.com