Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q
Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q
复制标题
DOI：
10.1007/s00439-001-0650-x
复制
发表时间：
2002-01-01
期刊：
影响因子：
5.3
通讯作者：
Schofield, PR
中科院分区：
文献类型：
--
作者：
Brodaty, H;Mitchell, P;Schofield, PR
特发性基底神经节钙化（IBGC）以放射学、神经学、认知和精神异常为特征。这些异常表型和异常基因之间的关系尚不清楚，尽管最近定位到染色体14q的IBGC易感位点（IBGC1）。我们从一个大的多代谱系中确定了两个兄弟姐妹，他们都被诊断为放射学上的IBGC、痴呆、双相情感障碍和帕金森病。我们评估了(1)其他家庭成员，以确定这四种表型是否作为IBGC的症状共同分离；(2)IBGC可能与染色体14q上的IBGC1位点或任何已知或潜在的痴呆基因相关。9名第二代和21名第三代成员接受了放射学、神经学、神经心理学和精神病学评估。我们对所有家族成员IBGC1位点的微卫星标记和ApoE、VLDL、alpha1-ACT、BChE-K、APP、PS1、PS2和tau基因的多态性进行了基因分型，并检测了这些基因与IBGC、痴呆和双相情感障碍的联系。10例有影像学颅内钙化的家庭成员中，除2例指标外，其余均正常。IBGC状态与严重认知障碍或痴呆（P=0.335）、双相情感障碍或帕金森病（P=1.0）无显著相关性。与IBGC1位点的连锁被排除。在测试的8个痴呆基因标记中，唯一的LOD阳性评分是ApoE ε 4多态性和痴呆/严重认知障碍。我们已经确定了一种形式的IBGC，其中钙化是独立于神经、认知和精神症状的遗传。这可能是这种疾病的第二个基因座。
Idiopathic basal ganglia calcification (IBGC) is characterised by radiological, neurological, cognitive and psychiatric abnormalities. The associations between these abnormal phenotypes and abnormal genes remain unclear despite the recent mapping to chromosome 14q of a susceptibility locus for IBGC (IBGC1). We identified two siblings, from a large multigenerational pedigree, who had both been diagnosed with radiological IBGC, dementia, bipolar affective disorder and Parkinsonism. We assessed (1) other family members to determine whether these four phenotypes were co-segregating as symptoms of IBGC, and (2) possible IBGC linkage to the IBGC1 locus on chromosome 14q or to any known or potential dementia genes. Nine second-generation and 21 third-generation members received radiological, neurological, neuropsychological and psychiatric assessments. We genotyped all family members for microsatellite markers at the IBGC1 locus and polymorphisms of the ApoE, VLDL, alpha1-ACT, BChE-K, APP. PS1, PS2 and tau genes and tested these for linkage to IBGC, dementia and bipolar disorder. Of the ten family members with radiological intracranial calcification, all except the two index cases were normal. There was no significant association between IBGC status and severe cognitive impairment or dementia (P=0.335) or bipolar affective disorder or Parkinsonism (P=1.0). Linkage to the IBGC1 locus was excluded. Of the eight dementia gene markers tested, the only positive LOD score was for the ApoE epsilon4 polymorphism and dementia/severe cognitive impairment. We have identified a form of IBGC in which calcification is inherited independently of neurological, cognitive and psychiatric symptoms. This may represent a second locus for this disorder.