Strikingly Different Clinicopathological Phenotypes Determined by Progranulin-Mutation Dosage
نویسندگان
چکیده
منابع مشابه
Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage.
We performed hypothesis-free linkage analysis and exome sequencing in a family with two siblings who had neuronal ceroid lipofuscinosis (NCL). Two linkage peaks with maximum LOD scores of 3.07 and 2.97 were found on chromosomes 7 and 17, respectively. Unexpectedly, we found these siblings to be homozygous for a c.813_816del (p.Thr272Serfs∗10) mutation in the progranulin gene (GRN, granulin prec...
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Mutations in presenilin-1 (PSEN1) cause autosomal dominant Alzheimer's disease and mutations in MAPT cause the familial tauopathy Frontotemporal dementia linked to chromosome 17 (FTDP-17). However, there have been reports of mutations in PSEN1 and MAPT associated with cases of FTD with ubiquitin-positive tau-negative inclusion pathology. Here, we demonstrate that the MAPT variants are almost ce...
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Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD) with ubiquitin and TAR DNA-binding protein 43 (TDP43)-positive pathology. The clinical presentation associated with GRN mutations is heterogeneous and may include clinical probable Alzheimer's disease. All GRN mutations identified thus far cause disease through a uniform disease mechanism,...
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Inheritance of non-genetic factors permits ancestral environmental history to inform the development of subsequent generations. This form of soft inheritance has been shown in mammals, yet the molecular underpinnings of this phenomenon are poorly understood. In the present article, we focus on gametic inheritance of non-genetic factors, utilizing examples of paternal transmission to explore the...
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Corticobasal syndrome is characterized by cortical dysfunction and L-dopa-unresponsive Parkinsonism, with asymmetrical onset of clinical presentation and evidence of atrophy and/or hypometabolism at neuroimaging. Recently, the heterogeneous pathologic substrate of corticobasal syndrome has been further expanded to include cases with pathologic diagnosis of frontotemporal lobar degeneration with...
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ژورنال
عنوان ژورنال: The American Journal of Human Genetics
سال: 2012
ISSN: 0002-9297
DOI: 10.1016/j.ajhg.2012.04.021