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Title: Novel optineurin frameshift insertion in a family with frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis
Authors: Dominguez, Jacqueline
Yu, Jeryl Tan
Tan, Jayne Yi
Ng, Arlene
De Guzman, Ma Fe
Natividad, Boots
Daroy, Ma Luisa
Cano, Jemellee
Yu, Justine
Lian, Michelle Mulan
Zeng, Li
Lim, Weng Khong
Foo, Jia Nee
Ng, Adeline S. L.
Keywords: Science::Medicine
Issue Date: 2021
Source: Dominguez, J., Yu, J. T., Tan, J. Y., Ng, A., De Guzman, M. F., Natividad, B., Daroy, M. L., Cano, J., Yu, J., Lian, M. M., Zeng, L., Lim, W. K., Foo, J. N. & Ng, A. S. L. (2021). Novel optineurin frameshift insertion in a family with frontotemporal dementia and parkinsonism without amyotrophic lateral sclerosis. Frontiers in Neurology, 12, 645913-.
Project: NRF-NRFF2016-03
MOHTA18may- 0003
Journal: Frontiers in Neurology
Abstract: Frontotemporal Dementia (FTD) is a common cause of Young Onset Dementia and has diverse clinical manifestations involving behavior, executive function, language and motor function, including parkinsonism. Up to 50% of FTD patients report a positive family history, supporting a strong genetic basis, particularly in cases with both FTD and amyotrophic lateral sclerosis (FTD-ALS). Mutations in three genes are associated with the majority of familial FTD (fFTD) cases - microtubule associated protein tau gene (MAPT), granulin precursor (GRN), and hexanucleotide repeat expansions in chromosome 9 open reading frame 72- SMCR8complex subunit (C9orf72) while mutations in other genes such as optineurin (OPTN) have rarely been reported. Mutations in OPTN have been reported mostly in familial and sporadic cases of ALS, or in rare cases of FTD-ALS, but not in association with pure or predominant FTD and/or parkinsonian phenotype. Here, we report for the first time, a family from the Philippines with four members harboring a novel frameshift insertion at OPTN (Chr 10:13166090 G>GA) p.Lys328GluTer11, three of whom presented with FTD-related phenotypes. Additionally, one sibling heterozygous for the frameshift insertion had a predominantly parkinsonian phenotype resembling corticobasal syndrome, but it remains to be determined if this phenotype is related to the frameshift insertion. Notably, none of the affected members showed any evidence of motor neuron disease or ALS at the time of writing, both clinically and on electrophysiological testing, expanding the phenotypic spectrum of OPTN mutations. Close follow-up of mutation carriers for the development of new clinical features and wider investigation of additional family members with further genetic analyses will be conducted to investigate the possibility of other genetic modifiers in this family which could explain phenotypic heterogeneity.
ISSN: 1664-2295
DOI: 10.3389/fneur.2021.645913
Rights: © 2021 Dominguez, Yu, Tan, Ng, De Guzman, Natividad, Daroy, Cano, Yu, Lian, Zeng, Lim, Foo and Ng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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