Neurodegenerative Diseases最新文献

{"title":"Age of Onset and Length of Survival of Queensland Patients with Amyotrophic Lateral Sclerosis: Details of Subjects with Early Onset and Subjects with Long Survival.","authors":"Robert J Nona,&nbsp;Zhouwei Xu,&nbsp;Gail A Robinson,&nbsp;Robert D Henderson,&nbsp;Pamela A McCombe","doi":"10.1159/000528875","DOIUrl":"10.1159/000528875","url":null,"abstract":"<p><strong>Introduction: </strong>The aims of the study were to document the characteristics of amyotrophic lateral sclerosis (ALS) patients in Queensland, to examine factors influencing age of onset, and survival, and to study those with early-onset (<45 years) disease and those with long (>5 years) survival.</p><p><strong>Methods: </strong>We studied subjects seen at the ALS Clinic at the Royal Brisbane and Women's Hospital. We recorded sex, age of onset, region of onset, length of survival, presence of family history, type of disease, and evidence of cognitive involvement. We analysed the influence of these features on age of onset and survival. We analysed the features of patients with early onset of disease and patients with long survival.</p><p><strong>Results: </strong>There were 855 ALS patients (505 males) in the cohort. The age of onset was lower in males than females, in patients with a family history of ALS compared to those without, and in patients with spinal onset compared to bulbar onset. Early-onset disease was seen in 10% of patients, and had a greater proportion of males, spinal onset, and classical ALS phenotype compared to late-onset disease. Survival was shorter in females, in patients with bulbar onset, and in patients with classical ALS. Long survival was seen in 18% of patients. Patients with long survival had younger age of onset, greater proportion of males, spinal onset, and fewer patients with classical ALS.</p><p><strong>Conclusion: </strong>Our study confirms that ALS is more prevalent in males and that spinal onset is more common than bulbar onset. Males have earlier onset but longer survival. We found that overall, patients with classical ALS have worse survival than ALS variants, but some patients who were considered to have classical ALS had long survival. This study confirms the similarity of ALS in our region to ALS in other geographical regions.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"104-121"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10627495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New editorship of Neurodegenerative Diseases.","authors":"","doi":"10.1159/000531607","DOIUrl":"10.1159/000531607","url":null,"abstract":"","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"87"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pivotal Time.","authors":"Gilles Allali","doi":"10.1159/000531867","DOIUrl":"10.1159/000531867","url":null,"abstract":"Neurodegenerative Diseases, founded two decades ago by Roger M. Nitsch and Christoph Hock [1], holds a crucial position in filling the gap between fundamental research and clinical applications. It is a great honor to succeed the esteemed founding editors and the accomplished former editor, Paul G. Unschuld, who have elevated the journal to its current level. The field of neurodegenerative diseases is currently experiencing a pivotal time. After the devastating COVID-19 killing countless older adults with neurodegenerative diseases and social isolation being imposed on older survivors, a new disabling condition known as long COVID has emerged, affecting the cognition of young and older adults. Besides the sad consequences of COVID-19, there is a recent hope with the revolutionizing disease-modifying therapies that are becoming available for patients with Alzheimer’s disease (AD). Interestingly, the founder editors of Neurodegenerative Diseasesmade a significant contribution to the development of diseasemodifying therapies for AD [2]. The SARS-CoV-2 pandemic had a worldwide impact (Fig. 1), destabilizing the healthcare systems and leaving a bitter taste as it neglected millions of older adults, particularly those with neurodegenerative diseases, even in the most developed countries, due to the lack of resources and knowledge. In April 2020, I remember evaluating at the Geneva University Hospitals’ ICU during a busy Friday evening a 75-year-old nuclear engineer with Parkinson’s disease, who was struggling with a severe SARS-CoV-2 infection. Remarkably, after 15 days of intubation, he was finally feeling better and able to breathe without respiratory assistance, allowing him the privilege to enjoy the Kiddush of Shabbat, the blessings performed at the beginning of the Friday evening Shabbat dinner; an unusual celebration for an ICU. Prepared with love by his wife, who was unfortunately prohibited from entering to the ICU for “safety” reasons, the patient was slowly eating and gave hope to his son, who stood by his father’s side, reciting together prayers welcoming the Shabbat. It was his last Shabbat. The religious man died 24 h later from a COVID-19 encephalopathy, one of the most devastating neurological complications of COVID19 [3]. On the next Monday, when I shared this sad news with my team, the young neuropsychologist, who had been diligently caring for the patient for 15 days, was totally devastated, falling into a deep burnout. Few months later, the same neuropsychologist experienced a mild SARS-CoV-2 infection but then suffered from a severe long COVID rendering her unable to care for her patients for several months. This story underscores how the pandemic has not only impacted patients and families but has also affected healthcare providers. Numerous reports have highlighted the alarming death rate among healthcare workers, either directly from SARS-CoV-2 infection [4] or from the indirect consequences of overwhelming pressure leading some","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"88-90"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ecological Validity of the Montreal Cognitive Assessment in Non-Demented Parkinson's Disease Patients.","authors":"Edoardo Nicolò Aiello,&nbsp;Alfonsina D'Iorio,&nbsp;Federica Solca,&nbsp;Silvia Torre,&nbsp;Eleonora Colombo,&nbsp;Alessio Maranzano,&nbsp;Alberto De Lorenzo,&nbsp;Valerio Patisso,&nbsp;Mauro Treddenti,&nbsp;Claudia Morelli,&nbsp;Alberto Doretti,&nbsp;Luca Maderna,&nbsp;Federico Verde,&nbsp;Roberta Ferrucci,&nbsp;Sergio Barbieri,&nbsp;Fabiana Ruggiero,&nbsp;Alberto Priori,&nbsp;Vincenzo Silani,&nbsp;Nicola Ticozzi,&nbsp;Gabriella Santangelo,&nbsp;Andrea Ciammola,&nbsp;Barbara Poletti","doi":"10.1159/000532115","DOIUrl":"10.1159/000532115","url":null,"abstract":"<p><strong>Background: </strong>The ecological validity of performance-based cognitive screeners needs to be tested in order for them to be fully recommended for use within clinical practice and research.</p><p><strong>Objectives: </strong>The objective of this study was to examine, within an Italian cohort of non-demented Parkinson's disease (PD) patients, the ecological validity of the Montreal Cognitive Assessment (MoCA) by assessing its association with (1) functional independence (FI), (2) quality of life (QoL), and (3) behavioural-psychological (BP) outcomes.</p><p><strong>Methods: </strong>Seventy-four non-demented PD patients were administered the MoCA and underwent motor functional - i.e., Unified Parkinson's Disease Rating Scale (UPDRS), Modified Hoehn-Yahr Scale (HY), and Schwab and England Scale (SES) -, behavioural and psychological - i.e., State- and Trait-Anxiety Inventory-Form Y (STAI-Y1/-Y2), Beck Depression Inventory (BDI), and Dimensional Apathy Scale (DAS) - and QoL evaluations - i.e., MOS 36-Item Short Form Health Survey (SF-36). Associations of interest against FI, QoL, and BP outcomes were tested via Bonferroni-corrected Pearson's/Spearman's correlations while covarying for demographics, disease duration as well as UPDRS-III, UPDRS-IV, and HY scores. Intake of psychotropic drugs was also covaried when assessing the association between the MoCA and BP/QoL measures.</p><p><strong>Results: </strong>MoCA scores were significantly associated with the SES (rs(73) = 0.34; p = 0.005) and the DAS-Executive (r(67) = -0.47; p &lt; 0.001), while not to other FI/BP outcomes and QoL measures.</p><p><strong>Conclusions: </strong>The MoCA is a valid estimate of daily life functional autonomy in non-demented PD patients, also reflecting apathetic features of a dysexecutive nature.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"159-163"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF Aβ40 and P-Tau181 Might Differentiate Atypical from Typical AD Phenotypes: Preliminary Evidence.","authors":"Federico Verde,&nbsp;Edoardo Nicolò Aiello,&nbsp;Eleonora Giacopuzzi Giacopuzzi Grigoli,&nbsp;Ilaria Milone,&nbsp;Antonella Dubini,&nbsp;Antonia Ratti,&nbsp;Barbara Poletti,&nbsp;Nicola Ticozzi,&nbsp;Vincenzo Silani","doi":"10.1159/000526888","DOIUrl":"https://doi.org/10.1159/000526888","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed at testing whether CSF levels of amyloid β42 (Aβ42), Aβ40, total tau, and phosphorylated tau (P-tau181) individually contribute to the identification of atypical phenotypes among a retrospective cohort of probable Alzheimer's disease (AD) patients diagnosed by means of the ratio between Aβ42 and Aβ40 (Aβ42/40).</p><p><strong>Methods: </strong>The retrospective study cohort comprised 50 probable AD patients diagnosed by means of the ratio between Aβ42 and Aβ40 (Aβ42/40) and for whom total tau and P-tau181 values were also available. Patients were clinically classified as typical, amnestic-predominant AD (N = 39; 16 males; mean age: 73.4 ± 7.6 years; mean disease duration: 27.4 ± 24.7 months), or atypical phenotypes (N = 11; 6 males; mean age: 70.2 ± 6.5 years; mean disease duration: 35.5 ± 24.9 months) - i.e., posterior cortical atrophy (N = 4), logopenic-variant primary progressive aphasia (N = 4), and behavioural variant AD (N = 3). A logistic regression allowed predicting the occurrence of atypical versus typical phenotypes based on age, sex, and Aβ42, Aβ40, total tau, and P-tau181 levels.</p><p><strong>Results: </strong>Atypical and typical AD patients were comparable for Aβ42/40 values. Only Aβ40 and P-tau181 levels positively (p = 0.015) and negatively (p = 0.019) predicted the occurrence of atypical AD phenotypes, respectively. Classification precision was of 86%, yielding excellent specificity (94.9%) but poor sensitivity (54.5%).</p><p><strong>Conclusions: </strong>The present study delivers promising, albeit preliminary, evidence on the utility of Aβ40 and P-tau181 CSF biomarkers in differentiating atypical from typical Aβ42/40-confirmed AD phenotypes, prompting further research and confirmation on larger cohorts.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"83-86"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9185142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-Phthalimidobenzenesulfonamide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: DFTs, 3D-QSAR, ADMET, and Molecular Dynamics Simulation.","authors":"Syeda Abida Ejaz,&nbsp;Ammara Fayyaz,&nbsp;Hafiz Mohammad Kashif Mahmood,&nbsp;Mubashir Aziz,&nbsp;Syeda Rabia Ejaz,&nbsp;Afrah F Alkhuriji,&nbsp;Wafa Abdullah I Al-Megrin,&nbsp;Abdullahi Tunde Aborode,&nbsp;Gaber El-Saber Batiha","doi":"10.1159/000527516","DOIUrl":"10.1159/000527516","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease is a form of dementia which affects majority of the people. It is characterized by memory loss and other cognitive function disabilities and is one of the most challenging neurodegenerative disorders to treat because of its progressive nature. The disease affects millions of people all around the world, and the number of those affected is expanding every day. In the previous study, the 4-phthalimidobenzenesulfonamide derivatives were synthesized as AChE and BChE inhibitors, and here, we were aiming to further reporting in silico studies of these compounds for efficient drug discovery process and to find out the potential lead compounds.</p><p><strong>Methods: </strong>In silico characterization included density functional theory (DFT) studies, 3D-QSAR, ADMET properties, molecular docking, and molecular dynamic simulations. The geometries of all derivatives were optimized using B3LYP method and 6-311G basis set.</p><p><strong>Results: </strong>The findings of the current study revealed that 4-phthalimidobenzenesulfonamide derivatives exhibited a reactive electronic property which is essential for anticholinesterase activity. Moreover, optimized structures were subjected to molecular docking studies with targeted protein. The compounds 2c and 2g showed excellent binding score of -37.44 and -33.67 kJ/mol with BChE and AChE, respectively, and exhibited strong binding affinity. The potent derivatives produced stable complex with amino acid residues of active pocket of both BChE and AChE. The stability of protein-ligand complexes was determined by molecular dynamic simulation studies, and results were found in correlation with molecular docking findings.</p><p><strong>Conclusion: </strong>Findings of the current study suggested that these derivatives are potent inhibitors of cholinesterase enzyme.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 3-4","pages":"122-138"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41101362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Age-Related Slow-Wave Sleep Alterations Onset Prematurely in the Tg2576 Mouse Model of Alzheimer's Disease.","authors":"Sedef Kollarik,&nbsp;Inês Dias,&nbsp;Carlos G Moreira,&nbsp;Dorita Bimbiryte,&nbsp;Djordje Miladinovic,&nbsp;Joachim M Buhmann,&nbsp;Christian R Baumann,&nbsp;Daniela Noain","doi":"10.1159/000527786","DOIUrl":"https://doi.org/10.1159/000527786","url":null,"abstract":"<p><strong>Introduction: </strong>Sleep insufficiency or decreased quality have been associated with Alzheimer's disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD.</p><p><strong>Methods: </strong>We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/electromyography headpieces into 6-month-old (plaque-free, n = 10) and 11-month-old (moderate plaque-burdened, n = 10) Tg2576 mice and age-matched wild-type (WT, 6 months old n = 10, 11 months old n = 10) mice and recorded vigilance states for 24 h.</p><p><strong>Results: </strong>Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-h period compared to WT mice at 6 but not at 11 months of age. Concomitantly, power in the delta frequency was decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, rendering a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 h in the overall sleep-wake phenotype at 11 months of age appears to be the result of changes in sleep-wake characteristics accompanying the healthy aging of WT mice.</p><p><strong>Conclusion: </strong>Therefore, our results indicate that at the plaque-free disease stage, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"55-67"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9279886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immunomodulatory Potential Role of Mesenchymal Stem Cells in Diseases of the Central Nervous System.","authors":"Rodrigo de Andrade Rufino,&nbsp;Laís da Silva Pereira-Rufino,&nbsp;Thays Cristina Silva Vissoto,&nbsp;Irina Kerkis,&nbsp;Adriana da Costa Neves,&nbsp;Marcelo Cavenaghi Pereira da Silva","doi":"10.1159/000528036","DOIUrl":"https://doi.org/10.1159/000528036","url":null,"abstract":"<p><strong>Introduction: </strong>Several studies indicate the role of mesenchymal stem cells (MSCs) as an important tool in regenerative medicine associated with injuries that affect the central nervous system (CNS). The MSCs have the capacity to differentiate into cells of the embryonic tissue, such as the mesoderm. So, these cells can be found in a variety of tissues. Also, the MSCs can release immunomodulatory and neurotrophic factors performance as inflammation mediators operating in injured tissue regeneration. Furthermore, they can differentiate into neural-like cells in vitro. Thereby, because of the high immunomodulatory role of MSCs, this review sought to describe the main immunomodulatory mechanisms performed by MSCs in CNS recovery after tissue injury or neurodegenerative diseases.</p><p><strong>Methods: </strong>PubMed and ScienceDirect were searched between January 2011 to March 2021, and 43 articles met the criteria of the review.</p><p><strong>Results: </strong>This systematic review indicates that MSCs were used in vivo experimental multiple sclerosis, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ischemic stroke, and traumatic brain injury. The treatment MSCs were usually from human origin, derived from bone marrow, and administered intravenously.</p><p><strong>Conclusion: </strong>It was shown that MSCs, independent from origin or administration pathway, can reduce inflammation and help in the recovery and preservation of injured neural tissue. Thus, the use of MSCs represents a potential therapeutic option in the treatment of neurological disorders mediated by inflammatory processes.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 2","pages":"68-82"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Autonomic Symptoms Predict Functional Decline in Parkinson's Disease Independent of Dopaminergic Therapy.","authors":"Cameron Miller-Patterson,&nbsp;Jesse Y Hsu,&nbsp;Lana M Chahine","doi":"10.1159/000525664","DOIUrl":"https://doi.org/10.1159/000525664","url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) has variable progression; identifying determinants of functional decline in PD is needed for accurate prognostication. Autonomic symptoms can result from dopaminergic therapy but may also independently predict functional decline.</p><p><strong>Methods: </strong>The sample included individuals with newly diagnosed PD in Parkinson's Progression Markers Initiative. Autonomic symptoms were measured with the Scales-for-Outcomes-in-Parkinson's-Disease-Autonomic (SCOPA-AUT). Presence/absence of autonomic symptoms for SCOPA-AUT total scale and seven subscales was defined, and baseline demographic/clinical data were compared between groups with and without autonomic symptoms. Time-to-functional-dependence, or Schwab-and-England Activities-of-Daily-Living (SE-ADL) ≤70, was compared between groups using hazard models, adjusting for covariates including time-varying levodopa-equivalent daily dosage. If a subscale was associated with a significant subhazard ratio (SHR), hazard models for items in that subscale were generated and gender was evaluated as an effect modifier.</p><p><strong>Results: </strong>399 participants were included. Over a median of 72 months (range 6-84), 91 (22.81%) reached SE-ADL ≤70. SCOPA-AUT total/gastrointestinal/urinary/pupillomotor scales were associated with SE-ADL ≤70; respective multivariable SHRs (95% CI, p value) were 1.98 (1.06-3.70, 0.03), 1.71 (1.04-2.81, 0.03), 1.94 (1.25-3.01, <0.01), 2.56 (1.24-5.31, 0.01). Individual items in the gastrointestinal and urinary scales drove associations. Urinary scale associations were seen in males only.</p><p><strong>Conclusions: </strong>Symptoms of gastrointestinal, urinary, pupillomotor dysfunction are associated with functional decline risk in PD, independent of dopaminergic therapy. Detailed assessments of autonomic symptomatology should be utilized in studies attempting to refine predictive models of PD progression.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":"22 1","pages":"15-23"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671814/pdf/nihms-1822986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9750579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Manifestations Associated with the Domain-Containing Protein 2 Gene Mutation in an Iranian Family with Spastic Paraplegia 54.","authors":"Abolfazl Yari,&nbsp;Shokoofeh Etesam,&nbsp;Shannaz Zarifi,&nbsp;Sepideh Parvizpour,&nbsp;Ebrahim Miri-Moghaddam","doi":"10.1159/000530375","DOIUrl":"10.1159/000530375","url":null,"abstract":"<p><strong>Introduction: </strong>Spastic paraplegia type 54 (SPG54) is an autosomal recessive disorder caused by bi-allelic mutations in the DDHD-domain-containing protein 2 (DDHD2) gene. Worldwide, over 24 SPG54 families and 24 pathogenic variants have been reported. Our study aimed to describe the clinical and molecular findings of a pediatric patient from a consanguineous Iranian family with significant motor development delay, walking problems, paraplegia, and optic atrophy.</p><p><strong>Methods: </strong>The patient was a 7-year-old boy with severe neurodevelopmental and psychomotor problems. Neurological examinations, laboratory tests, electroencephalography, computed tomography scan, and brain magnetic resonance scan (MRI) were carried out for clinical evaluation. Whole-exome sequencing and in silico analysis were undertaken to identify the genetic cause of the disorder.</p><p><strong>Results: </strong>The neurological examination showed developmental delay, spasticity in the lower extremities, ataxia, foot contractures, and deep tendon reflexes in the extremities. The computed tomography scan was normal, but MRI revealed corpus callosum thinning with atrophic changes in the white matter. The genetic study reported a homozygous variant (c.856 C&gt;T, p.Gln286Ter) in the DDHD2 gene. The homozygous state was confirmed by direct sequencing in the proband and his 5-year-old brother. This variant was not reported as a pathogenic variant in the literature or genetic databases and was predicted to affect the function of the DDHD2 protein.</p><p><strong>Conclusion: </strong>The clinical symptoms in our cases were similar to the previously reported phenotype of SPG54. Our results deepen the molecular and clinical spectrum of SPG54 to facilitate future diagnoses.</p>","PeriodicalId":19115,"journal":{"name":"Neurodegenerative Diseases","volume":" ","pages":"139-150"},"PeriodicalIF":3.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}