Study On MTMR9 And Non-specific Mental Retardation

Mental Retardation(MR)is a neuropsychiatric disorder that severely affects the health of children and adolescents.Non-Specific Mental Retardation(NSMR),one of common classification of MR,which characterized by significantly impaired intellectual and adaptive functioning comparing with their peers.The obvious family clustering phenomenon and a mass of genetic research work indicated that,genetic factor may be one of causal elements for NSMR.Recently,several mutation scanning reported that,some missense mutations of Myotubularin Related Protein 9(MTMR9)gene can lead to the occurrence of NSMR,and suspected that the genetic variants of MTMR9 may be closely related to NSMR.To investigate the association between MTMR9 gene genetic variants and NSMR,a 258 NSMR nuclear families and 721 individuals from Qinba Mountain region in China involved.Seven SNPs within MTMR9 gene region were chosen and genotyped with restricted fragment length polymorphisms(RFLP)and single-strand conformation polymorphism(SSCP)methods,combining with random Sanger sequencing technique verification.Then,a family-based association test(FBAT)was performed to analyze the association between genetic variation of MTMR9 gene and NSMR,through comparing the frequency of alleles and haplotypes transmit to effected subjects with the expected frequency by Mendelian principle,within families.The statistic power of this study also estimated by Quanto 1.2.4 software according to sample size,sample structure and the frequencies of alleles.The result showed that three SNPs of MTMR9 significant associated with NSMR in Qinba region(z = 1.926,p = 0.41 for rs4559208;z = 2.811,p = 0.005 for rs2164273;and z = 2.360,p = 0.018 for rs7815802,respectively).Alleles of these SNP(G,G and C)are more likely to be transmitted form carrier parents to their effected children.Haplotypes,constructed by positive SNPs,also shows a similar transmitting like single site.For instance,haplotypes constructed by three positive SNPs,whose distribution in family sample was obviously deviated from random principal(Chi 2(4)= 8.835,Global p = 0.065),G-G-C haplotype showed aberrant transmission in the family members of the patients(z = 2.505,p = 0.012).The G-G-C carrier showed a higher risk of NSMR(OR = 1.462,95% CI [1.01~2.09],p = 0.04)than other individuals.Other haplotypes consisted with two SNPs also demonstrated a similar transmitting feature.Furthmore,the Quanto 1.2.4 software analysis also indicated that,present study had a credible result with higher statistic power(> 93%),calculated by sample size,the number of nuclear family,and the frequency of alleles.In brief,this study provided,for the first time,evidence for the association between genetic variant of MTMR9 gene and NSMR in Chinese Han population.Missense mutations and other harmful events within MTMR9 gene region may cause different degrees of NSMR.Hence,a molecular analysis of this gene should be considered for patients presenting NSMR of unknown etiology.