Alzheimer's Disease and other Cognitive Disorders Unit, Institut d'Investigació Biomédica August Pi I Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain.
Eur J Neurol. 2010 Jul;17(7):994-6. doi: 10.1111/j.1468-1331.2010.02949.x. Epub 2010 Feb 10.
To describe a novel mutation (K239N) in the PSEN1 associated with familial Alzheimer's disease (AD).
The proband was a man who developed cognitive decline with marked behavioural abnormalities at age 57. At age 70, he was admitted into a psychiatric facility because of aggressiveness and a suicide attempt. Family history was consistent with autosomal dominant AD. One of the two other family members studied presented also with prominent behavioural symptoms at age 42 and has also been forced into a psychiatric facility because of aggressiveness at age 56. The remainder patient has presented a prototypical AD, but starting at age 71. Direct sequencing of PSEN1 in the three living affected members disclosed a heterozygous G to C transition in exon 7 of PSEN1 leading to the K239N mutation.
The K239N mutation is associated with autosomal dominant AD with a wide range of age of onset and incomplete penetrance at the age of 65, prominent behavioural features and slow progression.
描述与家族性阿尔茨海默病（AD）相关的 PSEN1 中的一种新突变（K239N）。
先证者为一名男性，57 岁时出现认知功能下降伴明显行为异常。70 岁时，因攻击性和自杀企图而被送进精神病院。家族史符合常染色体显性 AD。所研究的两个其他家族成员之一也在 42 岁时出现明显的行为症状，并因 56 岁时的攻击性而被迫住进精神病院。其余患者表现为典型的 AD，但从 71 岁开始。对 3 名存活的受累者 PSEN1 的直接测序显示 PSEN1 外显子 7 中的杂合 G 到 C 转换导致 K239N 突变。
K239N 突变与常染色体显性 AD 相关，发病年龄范围广泛，65 岁时不完全外显，有明显的行为特征和缓慢的进展。
