Objective To screen the fragilex mental retardation 1 (FMR1) gene mutations and explore the frequency of FMR1 gene mutation in the population with mental retardation in South China.Methods Seventy-two patients (65 males and 7 females) with suspected fragile X syndrome (FXS) in South China were enrolled in our hospitals from October 2009 to April 2014.The CGG trinucleotide repeats in 5'UTR of FMR1 gene and CCG trinucleotide repeats in FMR2 gene were screened respectively by PCR.Southern blotting and capillary electrophoresis sequencing were performed in male patients without normal target bands and suspected female patients;patients with normal CGG alleles were,then,performed exons and 3'-UTR ofFMR1 gene amplification and sequencing.The frequency of FMR1 gene mutation in patients with mental retardation in different countries and regions was compared with statistical analysis.Results Six pedigrees with full mutation (one female and five males being the probands),one pedigree (mother and son) with FMR1 gene deletion and one pedigree (mother and son) with mutation in the transition region were identified in 72 patients with mental retardation.The prevalence of total mutation was 9.7％ (7/72) and that in male patients was 9.2％ (6/65).These results showed significant differences in prevalence as compared with the results from different countries and areas (P＜0.05);there were no variations in 3'UTR ofFMR1 gene and FMR2 gene mutation in the patients with FXS-like phenotype.Conclusions FMR1 mutation frequency may be higher in mental retardation population in southem China as compared with that in developed countries or areas.Targeted screening on the unexplained mental retardation pedigrees (family history) can improve the diagnosis of FXS.Importantly,deletion mutations screening should also be performed in suspected FXS subjects with normal CGG repeats.

Objective:To observe the effect of bacteroides fragilis BF839 intervention on learning, memory and social novelty of fragile X-mental retardation gene 1 ( Fmr1) knockout (KO) mice. Methods:Thirty three-week-old Fmr1 KO mice were randomly divided into Fmr1 KO group ( n=15) and Fmr1 KO+BF839 group ( n=15). Mice in the Fmr1 KO group freely drank autoclaved tap water everyday; mice in the Fmr1 KO+BF839 group drank BF839 bacterial liquid (10 mL/d) everyday;11 wild-type mice freely drank autoclaved tap water everyday were set as controls (WT group). After 4 weeks of intervention, Morris water maze test was used to observe the differences in escape latency and frequencies of crossing the original platform among mice in each group; Three-chamber Social Interaction Test was used to observe the differences in contact frequencies and contact durations with unfamiliar mice among mice in each group. Results:On the 4 th d of experiment, the escape latency of mice in the Fmr1 KO group ([46.06±10.29] s) was significantly longer than that in the WT group ([33.39±12.02] s, P<0.05); the escape latency of mice in the Fmr1 KO+BF839 group ([28.39±9.07] s) was significantly shorter than that in the Fmr1 KO group ( P<0.05); the escape latency of mice in the Fmr1 KO+BF839 group was slightly shorter than that in the WT group without significant difference ( P>0.05). The frequencies of crossing through the original platform of mice in Fmr1 KO group (0.00[0.00, 1.00] time) was slightly less than that in WT group (1.00 [0.00, 1.00] time) without significant difference ( P>0.05); that in the Fmr1 KO+BF839 group (1.50[1.00, 2.00] times) was significantly larger than that in the Fmr1 KO group and WT group ( P<0.05). The contact frequencies of the mice in the Fmr1 KO group with unfamiliar mice (5.50[0.50, 12.75] times) was less than that in the WT group (7.00[4.00, 17.00] times) without significant difference ( P>0.05); that in the Fmr1 KO+BF839 group (23.00[16.00, 36.00] times) was significantly increased as compared with that in the Fmr1 KO group and WT group ( P<0.05). The contact duration of mice in the Fmr1 KO group with unfamiliar mice (9.50[0.50, 41.95] s) was significantly shorter than that in the WT group (142.00[65.00, 171.60] s, P<0.05); Fmr1 KO+BF839 group had significantly longer contact duration with unfamiliar mice (69.60 [50.40, 98.40] s) than Fmr1 KO group ( P<0.05); the contact duration of mice in Fmr1 KO+BF839 group with unfamiliar mice was shorter than that in WT group without significant difference ( P>0.05). Conclusion:Early BF839 intervention can significantly improve the learning, memory abilities and social novelty of Fmr1 KO mice, and even restore the Fmr1 KO mice to normal levels, which suggests that BF839 may become a new tool for treatment of fragile X syndrome and autism.