Clinical Features,gene Diagnosis And Pedigree Analysis Of Huntington Disease In Sichuan

Objective: To investigate the clinical characteristics of families with Huntington's disease in Sichuan,and to make gene diagnosis and family analysis.To provide genetic counseling for family members in order to avoid the passage of pathogenic genes.Methods: To collect the basic information,medical history,physical examination and imaging examination of Huntington's disease patients and some family members from March 2016 to March 2018 in Sichuan Provincial people's Hospital,and to draw a pedigree map.The IT15 gene CAG trinucleotide repeats were detected among participants.Using Mini-mental state examination(MMSE),Montreal cognitive assessment scale(MoCA),Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),Pittsburgh sleep quality index(PSQI)and Activities of daily living scale(ADL)to evaluate the cognitive function,anxiety,depression,sleep and ability of daily life of HD patients and some gene positive participants.The above data were analyzed.Results: A total of 24 individuals from four families participated in IT15 gene sequencing.Eight patients(6 males and 2 females)with HD were confirmed by gene sequencing.Among them,the age was 24~76(47.88 ±15.39)years old and the onset age was 23 ~57(39.38 ±9.84)years old.The course of disease was 1~31 years,and the number of abnormal CAG repeats was 41~ 54(46.75 ±4.03)in these HD patients.Seven patients(5 males and 2 females)were found to be presymptomatic.Among them,the age was 7~47(47.88 ±15.39)years old and the number of abnormal CAG repeats was 43~58(50.00 ±6.40).The normal CAG repeats were in the range of 12 to 24 times,with 17 and 20 being the most common.There were 10 dead HD patients in 4 families,the age of onset was 33 ~50(43.30 ±5.72)years old and the course of disease was 8~15 years.Pearson correlation analysis showed that there was a negative correlation between the number of CAG repeats and the age of onset(r =-0.967,P < 0.01).The ADL score was negatively correlated with the MMSE score(r =-0.930,P < 0.01)and the MOCA score(r =-0.932,P < 0.01).Spearman correlation analysis showed that the ADL score was positively correlated with the course of disease(r = 0.842,P < 0.01).A total of 4 times CAG repeats were amplified during the process of pedigree heredity,and the amplified fragments ranged from 2 to 10.There were three paternal inheritances and one maternal inheritance.Three families had typical family history and one family had negative history.In pedigree A,the onset age of the first generation was 50 years old,and the average onset age of the second generation was about 40 years old.However the average onset age of the third generation was about 36 years old.In pedigree C the first generation onset age is 40 years old,and the average onset age of the second generation is about 33 years old.In the third generation of pedigree C the onset age is 23 years old.At present,one proband and three presymptomatic patients are in childbearing age in all families,so it is suggested that genetic counseling should be carried out.All probands suffered from various degrees of involuntary movement and had rare non-motor symptoms such as anxiety,depression,apathy,personality change,sleep disorder,weight loss and so on.Patient without family history who suffered from involuntary movement were misdiagnosed as normal pressure hydrocephalus before further gene testing was confirmed.The typical imaging features of HD patients with long course of disease showed obvious nucleus putamen and atrophy of caudate nucleus,but there was no obvious change in early patients.Conclusion: Genetic detection is of great significance in the diagnosis of Huntington's disease,especially in atypical patients with negative family history.Amplification of CAG repeats exists in the process of passage of the pedigree and the patrilineal inheritance is dominant.There is genetic anticipation.CAG repeats can be used to predict the age of onset to a certain extent.In addition to typical involuntary movement,non-motor symptoms can also appear in the course of the disease.At present,there is no effective treatment for this disease,so genetic counseling and prenatal diagnosis are very important to avoid birth of a child with HD.