Novel missense mutation in charged multivesicular body protein 2B in a patient with frontotemporal dementia.
Novel missense mutation in charged multivesicular body protein 2B in a patient with frontotemporal dementia.
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DOI：
10.1097/wad.0b013e3181df20c7
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发表时间：
2010-10
影响因子：
2.1
通讯作者：
Momeni P
中科院分区：
文献类型：
--
作者：
Ferrari R;Kapogiannis D;Huey ED;Grafman J;Hardy J;Momeni P
额颞叶痴呆（FTD）是继阿尔茨海默病（AD）之后65岁以下人群痴呆的第二大主要原因。FTD在临床、病理学和遗传学上具有异质性，与位于17、9和3号染色体上的不同基因突变相关。在我们的研究中，我们报告了1例确诊为FTD的患者在带电多泡体蛋白2B（CHMP 2B）外显子6中发现了一种新的杂合g.26218G>A变异体，预计该变异体可导致氨基酸改变p.Ser187Asn。我们无法确定突变的遗传模式，因为我们无法获得先证者的遗传信息家族成员;那些接受筛查的人没有携带变异。我们在273名白人对照中没有发现这种变异，而在94名非洲裔美国人对照中有6名发现了这种变异。CHMP 2B中的大多数被认为是致病性的突变导致CHMP 2B蛋白的C-末端区域的部分缺失。根据以前的报告和我们目前的数据，错义突变似乎不太可能是致病性的。CHMP 2B突变的致病性需要进一步研究。
Frontotemporal Dementia (FTD) is the second major cause of dementia in persons under the age of 65 after Alzheimer’s disease (AD). FTD is clinically, pathologically and genetically heterogeneous and has been associated with mutations in different genes located on chromosomes 17, 9 and 3. In our study we report a novel heterozygous g.26218G>A variant in exon 6 of Charged Multivesicular body Protein 2B (CHMP2B), predicted to cause the amino acid change p.Ser187Asn, in one patient diagnosed with FTD. We were not able to determine the mode of inheritance of the mutation since we did not have access to the genetically informative family members of the proband; those who were screened did not carry the variant. We didn’t find this variant in 273 Caucasian controls while we did find it in 6 of 94 African American controls. Most of the mutations in CHMP2B which are considered pathogenic lead to partial deletion of the C-terminus region of CHMP2B protein. Based on previous reports and on our current data, missense mutations seem unlikely to be pathogenic. The pathogenicity of CHMP2B mutations requires further investigation.