Early-onset of Frontotemporal Dementia and Amyotrophic Lateral Sclerosis in an Albanian Patient with a c.1319C>T Variant in the UBQLN2 Gene
Mirko Baglivo1, Elena Manara1, *, Natale Capodicasa2, Paolo Enrico Maltese3, Liborio Stuppia4, Sandro Michelini5, Rita Compagna6, Bruno Amato6, Matteo Bertelli1
Identifiers and Pagination:Year: 2020
First Page: 25
Last Page: 31
Publisher Id: MEDJ-7-25
Article History:Received Date: 22/04/2020
Revision Received Date: 23/06/2020
Acceptance Date: 01/07/2020
Electronic publication date: 25/08/2020
Collection year: 2020
open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Frontotemporal Dementia (FTD) is the second most common cause of dementia under 65 years of age; it has a prevalence of 4-15 per 100,000 persons. The overt disease usually manifests in the sixth decade, and it is extremely rare to find affected patients in their twenties.
Here, we present the clinical and molecular genetic findings of an Albanian family with a patient with early-onset FTD and Amyotrophic Lateral Sclerosis (ALS).
Given the great variability of clinical presentation of FTD and the number of genes involved, targeted Next Generation Sequencing (NGS) was used to screen the DNA of the 27-year-old male patient. Segregation analysis was performed in available family members.
Results and Discussion:
A variant, consisting of a proline-leucine amino acid substitution in position 440, was identified in the UBQLN2 gene on the X-chromosome. This variant was previously reported as a variant of unknown significance in a 30-year-old female patient with amyotrophic lateral sclerosis. With the description of our case, we add evidence on its involvement, also in ALS-FTD. The variant is in a functional domain important for interaction with HSP70 and this, in turn, may impair the shuttling of proteins to the proteasome leading to an accumulation of protein aggregates. The variant was inherited from the unaffected mother, in line with the fact that incomplete penetrance has been widely described for this gene.
The present report adds information regarding one of 34 variants in the UBQLN2 gene reported so far in association with neurodegeneration and proposes a molecular pathogenesis of ALS-FTD in this patient.