PDF(Pubmed)
Abstract：
UNASSIGNED: MAPT variants are a known cause of frontotemporal dementia and Parkinsonian syndrome, of which progressive supranuclear palsy syndrome (PSP) is a rare manifestation.
UNASSIGNED: To report a novel MAPT variant in a PSP pedigree with autosomal dominant inheritance pattern, and to produce a literature review of PSP patients with MAPT variants.
UNASSIGNED: A comprehensive clinical, genetic, and molecular neuroimaging investigation was conducted on a 61 years-old female proband diagnosed with PSP. We also collected the clinical presentation data and history of the patient\'s pedigree, and performed further genetic analysis of 4 relatives, from two generations, with and without symptoms.
UNASSIGNED: The proband exhibited typical clinical manifestation of PSP. A cranial MRI revealed midbrain atrophy, and an FDG-PET scan suggested hypo-metabolic changes in caudate nucleus, left prefrontal lobe, both temporal poles, and midbrain. 18F-florzolo-tau-PET revealed tau-protein deposits in the thalamus and brainstem bilaterally. A gene test by whole-exome sequencing identified a novel MAPT variant [NM_005910.6, exon 11, c.1024G > A (p.E342K)], and the same variant was also identified in one affected relative and one asymptomatic relative, a probable pre-symptomatic carrier.
UNASSIGNED: The PSP pedigree caused by the novel MAPT (E342K) variant, expanded the mutational spectrum of MAPT.
UNASSIGNED: To report a novel MAPT variant in a PSP pedigree with autosomal dominant inheritance pattern, and to produce a literature review of PSP patients with MAPT variants.
UNASSIGNED: A comprehensive clinical, genetic, and molecular neuroimaging investigation was conducted on a 61 years-old female proband diagnosed with PSP. We also collected the clinical presentation data and history of the patient\'s pedigree, and performed further genetic analysis of 4 relatives, from two generations, with and without symptoms.
UNASSIGNED: The proband exhibited typical clinical manifestation of PSP. A cranial MRI revealed midbrain atrophy, and an FDG-PET scan suggested hypo-metabolic changes in caudate nucleus, left prefrontal lobe, both temporal poles, and midbrain. 18F-florzolo-tau-PET revealed tau-protein deposits in the thalamus and brainstem bilaterally. A gene test by whole-exome sequencing identified a novel MAPT variant [NM_005910.6, exon 11, c.1024G > A (p.E342K)], and the same variant was also identified in one affected relative and one asymptomatic relative, a probable pre-symptomatic carrier.
UNASSIGNED: The PSP pedigree caused by the novel MAPT (E342K) variant, expanded the mutational spectrum of MAPT.
摘要：
■MAPT变异是额颞叶痴呆和帕金森综合征的已知原因，其中进行性核上性麻痹综合征（PSP）是一种罕见的表现。
■为了报告具有常染色体显性遗传模式的PSP家系中的新型MAPT变体，并对具有MAPT变异的PSP患者进行文献综述。
■全面的临床，遗传,对一名诊断为PSP的61岁女性先证者进行了分子神经影像学检查。我们还收集了患者谱系的临床表现数据和病史，并对4个亲属进行了进一步的遗传分析，两代人，有和没有症状。
■先证者表现为典型的PSP临床表现。头颅核磁共振显示中脑萎缩,FDG-PET扫描显示尾状核的低代谢变化，左前额叶,两个时间极点，还有中脑.18F-florzolo-tau-PET显示双侧丘脑和脑干中的tau蛋白沉积。通过全外显子组测序进行的基因测试鉴定了一种新的MAPT变体[NM_005910.6，外显子11，c.1024G>A（p。E342K)],在一名受影响的亲属和一名无症状的亲属中也发现了相同的变异，可能是症状前的携带者。
■由新型MAPT（E342K）变体引起的PSP谱系，扩大了MAPT的突变谱。
■为了报告具有常染色体显性遗传模式的PSP家系中的新型MAPT变体，并对具有MAPT变异的PSP患者进行文献综述。
■全面的临床，遗传,对一名诊断为PSP的61岁女性先证者进行了分子神经影像学检查。我们还收集了患者谱系的临床表现数据和病史，并对4个亲属进行了进一步的遗传分析，两代人，有和没有症状。
■先证者表现为典型的PSP临床表现。头颅核磁共振显示中脑萎缩,FDG-PET扫描显示尾状核的低代谢变化，左前额叶,两个时间极点，还有中脑.18F-florzolo-tau-PET显示双侧丘脑和脑干中的tau蛋白沉积。通过全外显子组测序进行的基因测试鉴定了一种新的MAPT变体[NM_005910.6，外显子11，c.1024G>A（p。E342K)],在一名受影响的亲属和一名无症状的亲属中也发现了相同的变异，可能是症状前的携带者。
■由新型MAPT（E342K）变体引起的PSP谱系，扩大了MAPT的突变谱。
