Screening And Analysis Of Fibrillin-1 Gene (FBN1) Mutation In A Chinese Family With Isolated Ectopia Lentis And Association Study Of Schizophrenia And The Polymorphisms Of COMT Gene In A Chinese Han Population

Isolated ectopia lentis (EL) is a rare autosomal dominant inherited eye disordercharacterized by stretching or disruption of the lenticular zonular filaments leads todisplacement of the lenses. Isolated EL is associated with mutations in the gene FBN1.FBN1 gene located on chromosome 15q21, is about 235kb in size. FBN1 encodesfibrillin-1, a secreted 350kDa glycoprotein known to be a major component of10-12nm microfibrils.In this study, an EL family including 8 patients and 20 normal members fromNingbo, Zhejiang Province, China, were investigated. Polymerase chain reaction(PCR), denaturing high performance liquid chromatograph (DHPLC) analysis andDNA sequencing were used to screen FBN1 gene for sequence variations. A recurrentmutation, c.184C>T, was identified in exon 2 of FBN1, resulting in the change ofArginine to Cystine (R62C). Restriction fragment length polymorphism (RFLP)analysis confirmed that (i) the c.184C>T point mutation was co-segregated with allaffected individuals in this EL pedigree, and (ii) all EL patients were heterozygous forthe mutation. This mutation occurred in the "Fib-4-Cys" module that contains4-cysteine residues in the N-terminus of fibrillin-1.The results suggested that thispoint mutation might be the causative mutation of the EL cases and provided themolecular basis of classification, molecular diagnosis, prenatal diagnosis,preimplantation genetic diagnosis (PGD) and be helpful for the new drug discoveryand gene therapy of the disease.Part IIAssociation Study of Schizophrenia and the polymorphisms of COMTGene in a Chinese Han PopulationSchizophrenia is a common disease with complex mode of inheritance, greatefforts have been made to identify the susceptible genes. Catchol-O-methyltransferase(COMT) gene has long been considered as a candidate gene mainly because of tworeasons: Firstly, it encodes a key dopamine catabolic enzyme. Secondly it maps to thevelocardiofacial syndrome region of chromosome 22q11, which associated withschizophrenia predisposition. Numerous case-control and family-based studies havebeen conducted, majority of them focused on a functional Val158Met polymorphism(rs4680). Unfortunately, these studies have produced conflicting results. In a previousreport, Shifman et al found a three-marker haplotype (rs737865-rs4680-rs165599)showed a significant association with schizophrenia. In this study, we try to replicatetheir findings in Chinese Han population and failed to find any associations.