@article {732, title = {Presenilin-1 Mutations Are a Cause of Primary Lateral Sclerosis-Like Syndrome.}, journal = {Front Mol Neurosci}, volume = {14}, year = {2021}, month = {2021}, pages = {721047}, abstract = {

Background and Purpose: Primary lateral sclerosis (PLS) is a progressive upper motor neuron (UMN) disorder. It is debated whether PLS is part of the amyotrophic lateral sclerosis (ALS) spectrum, or a syndrome encompassing different neurodegenerative diseases. Recently, new diagnostic criteria for PLS have been proposed. We describe four patients of two pedigrees, meeting definite PLS criteria and harboring two different mutations in presenilin 1 ().

Methods: Patients underwent neurological and neuropsychological examination, MRI, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), amyloid-related biomarkers, and next-generation sequencing (NGS) testing.

Results: Four patients, aged 25-45 years old, presented with a progressive UMN syndrome meeting clinical criteria of definite PLS. Cognitive symptoms and signs were mild or absent during the first year of the disease but appeared or progressed later in the disease course. Brain MRI showed microbleeds in two siblings, but iron-related hypointensities in the motor cortex were absent. Brain FDG-PET showed variable areas of hypometabolism, including the motor cortex and frontotemporal lobes. Amyloid deposition was confirmed with either cerebrospinal fluid (CSF) or imaging biomarkers. Two heterozygous likely pathogenic mutations in (p.Pro88Leu and p.Leu166Pro) were found in the NGS testing.

Conclusion: Clinically defined PLS is a syndrome encompassing different neurodegenerative diseases. The NGS testing should be part of the diagnostic workup in patients with PLS, at least in those with red flags, such as early-onset, cognitive impairment, and/or family history of neurodegenerative diseases.

}, issn = {1662-5099}, doi = {10.3389/fnmol.2021.721047}, author = {V{\'a}zquez-Costa, Juan Francisco and Pay{\'a}-Montes, Mar{\'\i}a and Mart{\'\i}nez-Molina, Marina and Jaijo, Teresa and Szymanski, Jazek and Maz{\'o}n, Miguel and Sopena-Novales, Pablo and P{\'e}rez-Tur, Jordi and Sevilla, Teresa} } @article {21412950, title = {Phylogenetic and in silico structural analysis of the Parkinson disease-related kinase PINK1.}, journal = {Human mutation}, volume = {32}, year = {2011}, month = {2011 Apr}, pages = {369-78}, abstract = {

Parkinson disease (PD) is the second most common neurodegenerative disorder and is characterized by the loss of dopaminergic neurons in the substantia nigra. Mutations in PINK1 were shown to cause recessive familial PD, and today are proposed to be associated with the disease via mitochondrial dysfunction and oxidative damage. The PINK1 gene comprises eight exons, which encode a ubiquitously expressed 581 amino acid protein that contains an N-terminal mitochondrial targeting domain and a serine/threonine protein kinase. To better understand the relationship between PINK1 and PD we have first analyzed the evolutionary history of the gene showing its late emergence in evolution. In addition, we have modeled the three-dimensional structure of PINK1 and found some evidences that help to explain the effect of some PD-related mutations in this protein{\textquoteright}s function.

}, doi = {10.1002/humu.21444}, author = {Cardona, Fernando and S{\'a}nchez-Mut, Jose Vicente and Dopazo, Hern{\'a}n and P{\'e}rez-Tur, Jordi} }