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Aging and disease    2019, Vol. 10 Issue (5) : 1003-1011     DOI: 10.14336/AD.2018.0911
Orginal Article |
Clinical and Genetic Profiles in Chinese Patients with Huntington’s Disease: A Ten-year Multicenter Study in China
Hong-Lei Li1, Xiao-Yan Li1, Yi Dong1, Yan-Bin Zhang2, Hong-Rong Cheng1, Shi-Rui Gan2, Zhi-Jun Liu3, Wang Ni1, Jean-Marc Burgunder4, X. William Yang5, Zhi-Ying Wu1,6,*
1Department of Neurology and Research Center of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, China.
2Department of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
3Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
4Swiss Huntington’s Disease Centre, Siloah, Gümligen and, Department of Neurology, University of Bern, Bern, Switzerland.
5Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Brain Research Institute, David Geffen School of Medicine, University of California at Los Angeles, CA, USA.
6Joint Institute for Genetics and Genome Medicine between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou, China
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Abstract  

Huntington’s disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG triplet repeats expansion in exon 1 of the Huntingtin gene (HTT). In China, HD is considered to have a low prevalence. The goal of this study was to describe the clinical characteristic and genetic profiles of HD in a Chinese cohort. A total of 322 individuals with expanded CAG repeats were consecutively recruited from the neurologic clinics of three medical centers in Southeastern China between 2008 and 2018. Among them, 80 were pre-symptomatic mutation carriers and 242 were symptomatic patients. The mean age at onset (AAO), defined here as the age at motor symptom onset, of the 242 manifest HD individuals was 40.3 ± 11.9 years and the mean CAG repeat length was 46.1 ± 7.5 in the group of symptomatic patients. Initial symptoms were abnormal movements in 88.8% of the patients with psychiatric symptoms in 6.2%, cognitive impairment in 3.3% and others in 1.7%. The AAO of motor was negatively correlated with the CAG repeat length in an exponential regression analysis (R 2 = 0.74, P<0.001). Analysis of 46 parent-child pairs showed that the CAG repeat length was longer in the offspring group (45.8 ±7.6) than in the parent group (43.8 ±3.0) (p=0.005). Overall, this study provides clinical and genetic profiles in a cohort of Chinese patients with HD, which should contribute to a better understanding of this disorder.

Keywords Huntington’s disease      Chinese population      phenotype      genotype     
Corresponding Authors: Wu Zhi-Ying   
About author:

Jean-Marc Burgunder is currently a visiting professor at Sichuan University (Chengdu), Central South University (Changsha) and Sun Yat Sen University (Guangzhou) in China.

Just Accepted Date: 22 September 2018   Issue Date: 27 September 2019
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Li Hong-Lei
Li Xiao-Yan
Dong Yi
Zhang Yan-Bin
Cheng Hong-Rong
Gan Shi-Rui
Liu Zhi-Jun
Ni Wang
Burgunder Jean-Marc
Yang X. William
Wu Zhi-Ying
Cite this article:   
Li Hong-Lei,Li Xiao-Yan,Dong Yi, et al. Clinical and Genetic Profiles in Chinese Patients with Huntington’s Disease: A Ten-year Multicenter Study in China[J]. Aging and disease, 2019, 10(5): 1003-1011.
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http://www.aginganddisease.org/EN/10.14336/AD.2018.0911     OR     http://www.aginganddisease.org/EN/Y2019/V10/I5/1003
Number
Patients322
 Manifest HD242
 Premanifest HD80
Family238
 Clear transmit mode178
 Paternal/ Maternal95/83
 Uncertain family history34
 Unknown family history26
CAG available309
Table 1  The profile of persons with HD in our cohort.
Figure 1.  The geographical distribution of HD patients. Most patients were from Southeast China.
AAO (years)CAGAge at diagnosis (years)DOD (years)

Mean (SD)RangeMean (SD)RangeMean (SD)RangeMean (SD)Range
Total (n=242)40.3 (11.9)4-7146.1 (7.5)38-10445.7 (12.4)7-835.4 (4.3)0.25-30
 male39.7 (12.8)8-7146.5 (8.0)39-10445.1 (13.4)10-835.5 (4.4)0.25-27
 female41.0 (11.0)4-6045.6 (6.9)38-9246.4 (11.2)7-685.4 (4.2)0.25-30
Juvenile HD (n=15)14.5 (4.8)4-2067.0 (16.8)46-10420.9 (9.3)7-426.4 (6.9)1-27
 male14.8 (4.2)8-2065.8 (18.6)46-10421.2 (10.2)10-426.4 (8.3)1-27
 female14.0 (6.2)4-1969.0 (14.8)56-9220.4 (8.3)7-286.4 (3.3)3-10
Adult HD (n=220)41.4 (9.4)21-5944.9 (3.6)39-5846.7 (10.1)23-685.3 (4.1)0.25-30
 male40.7 (9.8)21-5945.2 (3.5)39-5846.1 (10.6)23-685.4 (3.9)0.25-23
 female42.0 (9.1)21-5944.6 (3.4)40-5447.3 (9.5)26-685.3 (4.3)0.25-30
Elderly-onset HD (n=7)63.7 (4.8)60-7139.3 (0.9)38-4169.6 (6.7)63-835.8 (3.2)3-12
 male63.7 (4.9)60-7139.3 (0.9)38-4170.8 (7.7)63-835.6 (3.8)3-12
 female606038.538-3966.565-686.55-8
Table 2  Age at motor onset and CAG repeats among juvenile HD, adult HD and elder HD.
Figure 2.  Clinical and genetic features of Chinese patients with HD. A) Frequency distribution of age at onset (AAO) in Chinese HD patients (n=242). The AAO occurred mainly on 40 years of age. B) Spectrum of manifest HD with initial symptom (n=242). Chorea was the most frequent initial symptom in manifest HD, accounting for 80.6%. The others were atypical motor symptom and cognitive or psychiatric symptom. C) Frequency distribution of CAG repeats number with normal and expanded range in affected individuals with HD (n=306). D) Relationship between AAO and number of CAG repeats on the larger allele of HTT gene (n=242). The CAG repeats could explain approximately 74% of variance in AAO.
CAG RepeatsChinese cohorts (n=232)
Dutch cohort (n=755)
No. of patientsMedian AAO (y)95%CINo. of patientsMedian AAO (y)95% CI
<=40136059-62216855-81
41195045-53286558-72
423250.547-52906460-68
433249.544-49806056-64
44274240-441015552-58
452239.537-411045047-53
46173833-401004543-47
471435.532-42634139-43
48133331-39503735-39
4993226-45343836-40
5053120-39193430-38
512294-5483327-39
5252822-34112919-29
>=532219.516-23462320-26
Table 3  Median AAO for each number of CAG repeats in Chinese patients and Dutch patients.
Genetic and clinical featuresMainlandThai [14]Dutch [12]Korean [17]Mexican [16]African [6]
Expanded CAGMean46.143.546.045.447.244.5
SD7.53.04.04.75.44.0
Range38-10439-4839-7140-5837-10637-57
P value/0.150.800.580.01*0.21
AAO (years)Mean40.337.847.046.537.4N
SD11.98.315.012.712.9N
Range4-7127-584-8624-692-78N
P value/0.38<0.001*0.004*0.002*/
Initial symptomMotor88.8%NN89%#53.0%N
Behavior6.2%NN36%#30.0%N
Cognition3.3%NN28%#3.5%N
Cohort number242186143669137
Table 4  The number of CAG repeats, AAO and initial symptoms among different countries.
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