| Background and AimsMental retardation, one of the major birth defects, is a serious health hazard ofchildren’s syndrome. It has become a worldwide social problem because of its complexetiology and great harm to human with a high incidence of about2-3%around the world.Mental retardation is life-long pain to patients, but also a heavy financial burden for thefamily and the community,therefore studies on the screening and the pathogenesis of MRobviously attract much world’s attention.Complex causes of mental retardation includ bothexternal environment and internal genetics. In recent years, genetic factors in the etiologybecome more obvious,including various types of chromosomal abnormalities, single geneor gene abnormalities.However, the mechanism of nearly50%of MR remains unknown astechnical limits. Therefore, in-depth study of the pathogenesis,genetic screening anddiagnosis of mental retardation, are effective ways to reduce and eliminate the risk ofre-birth risk populations, and to prevent and cure the mental disorders.This study aims:(1)to screen372cases with mental retardation in genetic methods and analyze the candidategenes (ALDOA, TBX6, CYFP1, Nde1) related closely with unexplained mental retardationpatients.(2) to uncover the genetic mechanism of two MR cases with special chromosomekaryotype.MethodsG-banding karyotype analysis and multiplex ligation-dependent probe amplification(MLPA) were used for genetic screening for patients with mental retardation. MultiplexPCR method was established and used to analyze four candidate genes (ALDOA, TBX6,CYFP1, Nde1) on16p11.2,16p13.11,15q11.2from mental retardation patients.(2)Multiplex ligation-dependent probe amplification (MLPA), microarray comparativegenomic hybridization (Array CGH), single nucleotide polymorphism-based genotypingmicroarray (Array SNP) and short tandem repeat (STR) were integrated and used to analyzethe genetic verification of two special MR patients. Results1. About20.96%(78/372) and2.0%(7/372) of mental retardation patients were withabnormal karyotype and small subtelomeric rearrangements, respectively. Result from copynumber of high incidence of in candidate genes by the genetic screening showed that1casewas suspicious positive, the remaining were negative cases.2. We describe a5-year-old girl presented with mental retardation features. Conventionalkaryotyping revealed a novel unidirectional translocation t(11;9)(p15;p24). HumanCytoSNP-12Chip analysis identified a8M heterozygosis deletion from9p24.3to9p24.1,5M homozygousdeletion from9p24.1to9p23and12.5M duplication from9p23to9p21.2. The karyotype wasdescribed as45,XX,psu dic(9:11)(11qter->cen->11p15::9p24->cen->9qter), which was reported forthe first time here. A case of extra marker chromosome karyotype,47,XY,+mar was foundin this study. MLPA analysis showed that the additional marker chromosome was derivedfrom maternal chromosome15. The aCGH analysis revealed the genome copy numbervariation region was15q11-13, size9.8Mb, locus:20477397-30298155.Conclusion1. The construction of the reasonable and effective diagnosis system of the heritagemental retardation can raise the detection rate of the mental retardation,which playsignificance a lot in sudying and rsearching the pathogenisis of the mental retardation indepth.The multiplex PCR screening for candidate genes with intellectual disabilitiesestablished this study was proved to be a simple, economical and creative method,but needverification.2. The apparently balanced de novo translocations could produce cryptic deletions orduplications, and the precise mapping of the abnormal area may improve clinical management. Thedeletion and duplication of9p were associated with mental retardation. The increase in genecopy number replication at15q11-13region9.8Mb is also closely related to mentaldisorders. Integration of a variety of molecular genetic testing techniques is benefit formutual validation test results and can help improve the diagnosis of mental retardation. |
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