MAPT p.V363I mutation A rare cause of corticobasal degeneration

被引：15

作者：

Ahmed, Sarah ^{[1
]}

Fairen, Monica Diez ^{[2
,3
,4
]}

Sabir, Marya S. ^{[1
]}

Pastor, Pau ^{[2
,3
,4
]}

Ding, Jinhui ^{[5
]}

Ispierto, Lourdes ^{[6
]}

Butala, Ankur ^{[7
]}

Morris, Christopher M. ^{[8
]}

Schulte, Claudia ^{[9
,10
]}

Gasser, Thomas ^{[9
,10
]}

Jabbari, Edwin ^{[11
]}

Pletnikova, Olga ^{[12
]}

Morris, Huw R. ^{[11
,13
]}

Troncoso, Juan ^{[12
]}

Gelpi, Ellen ^{[14
,15
]}

Pantelyat, Alexander ^{[7
]}

Scholz, Sonja W. ^{[1
,7
]}

机构：

[1] NINDS, Neurodegenerat Dis Res Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[2] Univ Hosp Mutua Terrassa, Movement Disorders & Memory Unit, Barcelona, Spain

[3] Univ Hosp Mutua Terrassa, Dept Neurol, Barcelona, Spain

[4] Fundacio Recerca Biomed & Social Mutua Terrassa, Barcelona, Spain

[5] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA

[6] Hosp Univ Germans Trias, Neurol Serv, Badalona, Spain

[7] Johns Hopkins Univ, Med Ctr, Dept Neurol, Baltimore, MD 21218 USA

[8] Newcastle Univ, Newcastle Inst Ageing, Campus Ageing & Vital, Newcastle Upon Tyne, Tyne & Wear, England

[9] Univ Tubingen, Hertie Inst Clin Brain Res, Ctr Neurol, Dept Neurodegenerat Dis, Tubingen, Germany

[10] German Ctr Neurodegenerat Dis, Tubingen, Germany

[11] UCL, Inst Neurol, Dept Mol & Clin Neurosci, London, England

[12] Johns Hopkins Univ, Med Ctr, Dept Pathol Neuropathol, Baltimore, MD 21218 USA

[13] Inst Neurol, Dept Clin Neurosci, Royal Free Campus UCL, London, England

[14] Univ Barcelona, IDIBAPS, Hosp Clin, Neurol Tissue Bank, Barcelona, Spain

[15] Med Univ Vienna, Inst Neurol, Vienna, Austria

来源：

NEUROLOGY-GENETICS | 2019年 / 5卷 / 04期

关键词：

TAU GENE; FREQUENCY; MISSENSE;

D O I：

10.1212/NXG.0000000000000347

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Objective Patients with corticobasal syndrome (CBS) present with heterogeneous clinical features, including asymmetric parkinsonism, dyspraxia, aphasia, and cognitive impairment; to better understand the genetic etiology of this rare disease, we undertook a genetic analysis of microtubule-associated protein tau (MAPT). Methods We performed a genetic evaluation of MAPT mutations in 826 neurologically healthy controls and 173 cases with CBS using the Illumina NeuroChip genotyping array. Results We identified 2 patients with CBS heterozygous for a rare mutation in MAPT (p.V363I) that is located in the highly conserved microtubule-binding domain. One patient was pathologically confirmed and demonstrated extensive 4-repeat-tau-positive thread pathology, achromatic neurons, and astrocytic plaques consistent with corticobasal degeneration (CBD). Conclusions We report 2 CBS cases carrying the rare p.V363I MAPT mutation, one of which was pathologically confirmed as CBD. Our findings support the notion that this rare coding change is pathogenic.

引用

页数：8

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