Genetic And Clinical Characteristics Analysis Of Southeast Han Chinese Patients With Huntington Disease

Objective: To analysis the genetic and clinical features of Han patients withHuntington’s disease from southeastern China.Methods: A total of174cases of HD subjects from128families were collected.Using the polymerase chain reaction (polymerase chain reaction, PCR) to amplify theExon1of HTT gene and the product was direct sequencing after direct purification orgel extraction purification to detect (CAG)n copy number. We retrospectivelyanalyzed the clinical data of the subjects.Results: The average (CAG)n copy number of abnormal allele was44.32±1.92(36~104)，which was mainly within41times to48times. The average (CAG)n copynumber of normal allele was17.85±2.86(14~26) and the most common normal(CAG)n repeat size was17and18.93.8%of patients have a positive family history.The average number of CAG expansion was0.27±1.68(-3to3) in the pedigreesfrom maternal transmission, but it was increased to5.92±9.95(-3to29) in pedigreesfrom paternal transmission. Abnormal (CAG)n copy number, accounted forapproximately60.5%variance of age at onse（tAAO）, was negatively correlated withthe age at onset in adult HD patients. Chorea movement was the main onset symptomin adult HD, while JHD (Juvenile HD, JHD) presented with atypical clinicalmanifestations. The average size of abnormal (CAG)n repeat number was47.29±9.73in patients with paternal inheritance, but it was45.31±3.37in patients withmaternal inheritance. AAO was no significant difference between patients fromdifferent genetic background.(CCG)8of the abnormal allele was correlated withgreater abnormal (CAG)n copy number and the average CAG repeat number was51.85±13.80(42to82).Conclusion:1. The method of sequencing after direct purification or gel extraction purificationof PCR products can more accurately detect the (CAG)n copy number, which can effectively avoid the possible deviation during the restructuring process.2. The pathogenic (CAG)n copy number of Han HD patients from southeasternChina was mainly distributed in the range of41to48. The more common normal(CAG)n copy number was17and18. The frequency of (CAG) n distribution wasconsistent with other populations.3. The frequency of JHD from southeast Han Chinese population was consistentwith other populations, while the frequency of patients with onset before the age of10was higher than other groups.4. Adult HD patients presented with more typical clinical manifestations. JHDpresented with such atypical clinical manifestations that it was difficult to diagnoseduring early stage of the disease. Paternal inheritance was the dominant geneticpattern in JHD patients.5. The range of CAG amplification was small in the maternal transmission andgreater expansion occurred in the paternal transmission.6The pattern of inheritance will affect the abnormal (CAG)n copy number.Compared to maternal inheritance, paternal inheritance was corrected with greaterpathogenic (CAG)n copy number. Although AAO was no significant differencebetween patients from different genetic background, it still needs to further analysiswith large sample.7The abnormal (CAG)n copy number was negatively correlated with the age atonset.(CAG)n copy number,can only explain about60.5%variation of AAO, wasnot an independent predictors for AAO.8(CCG)n polymorphism of the abnormal allele might affect (CAG)n repeatsequence length.(CCG)8was related with greater (CAG)n repeat number, whichsuggested that (CCG)8of the abnormal allele might be a risk factor of HD patientsduring CAG expansion.