Applying Recombinant DNA Technology To Detect CAG Trinucleotide Repeats Of MJD1 Gene And Performing Prenatal Diagnosis Of SCA3/MJD

Background Hereditary spinocerebellar ataxias(SCAs)are a group of neurodegenerative disease,which shares high clinical and genetic heterogeneity and is characterized by a wide range of clinical manifestations,including cerebellar ataxia,pyramidal and extrapyramidal signs,progressive external ophthalmoplegia and dystonia with rigidity, and distal muscular atrophies.Most of the patients are of an autosomal dominant inheritance trait.There're at least 28 genotypes of SCAs which display autosomal dominant inheritance.Among them,18 genes responsible for the disease have been identified,including SCA1,SCA2, MJD1,PLEKHG4,SPTBN2,CACNA1A,SCA7,SCAB,SCAIO,TTBK2. PPP2R2B,KCNC3,PRKCG,ITPR1,CNIN4,TBP,FGF14 and DRPLA. The mutation of MJD1 gene cause SCA3/MJD.There are CAG repeats in exon 4 of MJD1.The normal and abnormal range of CAG repeats is 12-40 and 51-86 respectively.So the key to diagnosis SCA3/MJD is to detect the CAG repeats exactly and directly.Objective To establish exact and direct-viewing detection platform for CAG trinucleotide repeats of MJD1 gene by Recombinant DNA Technology;To perform the diagnosis of 35 SCA3/MJD patients and the first prenatal diagnosis of SCA3/MJD in mainland China.Methods Applying Recombinant DNA Technology to detect the CAG repeats of MJD1 gene in 35 SCA3/MJD patients and 10 healthy volunteers in mainland china and performing the first prenatal diagnosis of SCA3/MJD in mainland China. Results we detected the CAG trinucleotide repeats size of MJD1 gene exactly and directly in 35 SCA3/MJD patients and 10 healthy controls.In these patients,the range of CAG repeats of MJD1 gene is 65-81 and we identified CAG/CAA and CAG/TAG polymorphisms in the CAG repeats of MJD1 gene in Chinese SCA3 /MJD patients.In the prenatal diagnosis,the CAG repeats ofMJD1 gene of the proband and the proband's father and the proband's fetal were 81 repeats,74 repeats and 79 repeats respectively.We notified that intergenerational instability of the expanded CAG repeats is more significant in patemal transmission than in maternal transmission.Conclusionsâ‘ .Establish the mutation detection platform for CAG trinucleotide repeat ofMJD1 gene by Recombinant DNA Technology.â‘¡.Perform the first prenatal diagnosis of SCA3/MJD in mainland China.