Novel mutation in the ABCA1 gene identified in a chinese patient with dementia and atherothrombotic cerebral infarction.
BACKGROUND
To date, 81 mutations of ATP-binding cassette transporter 1 (ABCA1) have been reported. However, no ABCA1 mutation has been reported in the Chinese population.


METHODS
We used direct sequencing to screen for ABCA1 mutations in 72 patients with both atherosclerotic cerebral infarction (ACI) and plasma high-density lipoprotein cholesterol (HDL-C) < 0.8 mmol/l. The functionality of the mutation was verified using 200 unrelated controls and 76 patients with ACI and normal HDL-C by PCR-RFLP analysis.


RESULTS
One patient with dementia prior to ACI was found to carry the heterozygous Y2206D mutation, which has not been reported previously. The patient had a medical history of atherosclerosis in the coronary and carotid arteries going back 40 years and splenohepatomegalia for 13 years, with a low plasma HDL-C level (0.66 mmol/l) and apolipoprotein A1 level (0.61 mmol/l). During the past decade, he had developed symptoms of dementia. Sixteen months prior to the study, he was admitted to hospital for an ACI.


CONCLUSIONS
The results suggest that this patient is most likely a patient with familial hypoalphalipoproteinemia and that the Y2206D mutation may be associated with not only a lower level of HDL-C, but also with dementia.
Department of Neurology and Institute of Neurology, First Affiliated Hospital, Center of Neuroscience, Fujian Medical University, Fuzhou, China.
Xie-Hua
XH
Xue
Ning
N
Wang
Yi
Y
Lin
Gui-Xian
GX
Zhao
Ling
L
Fang
Shenxing
S
Murong
Zhi-Ying
ZY
Wu
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002544:Cerebral Infarction / Q000208:ethnology / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D003704:Dementia / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D052456:Hypoalphalipoproteinemias / Q000208:ethnology / Q000235:genetics; D002537:Intracranial Arteriosclerosis / Q000208:ethnology* / Q000235:genetics*; D020767:Intracranial Thrombosis / Q000208:ethnology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017354:Point Mutation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL