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.

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

© 2016 Tohoku University Medical Press

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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