Clinical and neuropathological variability in the rare IVS10 + 14 tau mutation

Maxwell, Selena P.; Cash, Meghan K.; Rockwood, Kenneth; Fisk, John D.; Darvesh, Sultan

doi:10.1016/j.neurobiolaging.2021.01.004

Cited by 1 publication

(1 citation statement)

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“…A recent study has discovered an increased tau-microtubule interaction caused by both mutations, thus describing a new and unique mechanism [6,7]. Carriers of MAPT mutations may have variable clinical phenotypes, with most patients presenting with behavioral variant FTD (bvFTD) and other clinical phenotypes, ranging from Alzheimer disease (AD)-like to corticobasal syndrome [8]. The patient with the Q336H mutation had a clinical phenotype of bvFTD, and although pathogenicity was confirmed for the mutation, segregation has not been studied in the previous family [3].…”

Section: Introductionmentioning

confidence: 99%

MAPT Q336H mutation: Intrafamilial phenotypic heterogeneity in a new Italian family

Villa

Rossi

Bizzozero

et al. 2022

Euro J of Neurology

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Background and purpose: Q336H is a rare MAPT mutation, previously found in a single patient with behavioral variant frontotemporal dementia and tau pathology (Pick bodies).Here, we describe the clinical characteristics of two members of a new family carrying the Q336H MAPT mutation.Methods: Clinical, genetic, and neuroradiological assessment and follow-up of the proband were made.Results: At age 37 years, the proband developed naming and object recognition impairment, due to a lack of knowledge. After 3 years, he developed behavioral disorders.Magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography showed the involvement of the left temporal pole. A diagnosis of semantic variant primary progressive aphasia (svPPA) was made. At follow-up after 6 and 12 months, a rapid worsening of cognitive deficits occurred. His parent presented, at age 65 years, slowly progressive memory deficits without behavioral impairment, and, on MRI, evidence of mesial temporal atrophy, consistent with a clinical diagnosis of Alzheimer disease (AD).Conclusions: This is the second family carrying the MAPT Q336H mutation reported so far. We showed that svPPA and AD-like phenotype can be associated with this mutation. A wide clinical variability exists at the intrafamilial level for Q336H MAPT mutation, pointing to genetic and/or environmental influencing factors on disease expression. We also confirmed that svPPA can be associated with MAPT mutations, suggesting that this gene should be analyzed also in patients with svPPA, especially with early onset. In addition, an AD-like phenotype may be associated with this mutation, suggesting its different effects on protein misfolding and aggregation.

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