Medicine and Health Sciences Commons^™

Epigenetic Clock Explains White Matter Hyperintensity Burden Irrespective Of Chronological Age, Joan Jiménez-Balado, Carolina Soriano-Tárraga, Et Al.

2020-Current year OA Pubs

In this manuscript we studied the relationship between WMH and biological age (B-age) in patients with acute stroke. We included in this study 247 patients with acute stroke recruited at Hospital del Mar having both epigenetic (DNA methylation) and magnetic resonance imaging data. WMH were measured using a semi-automated method. B-age was calculated using two widely used methods: the Hannum and Horvath formulas. We used multiple linear regression models to interrogate the role of B-age on WMH volume after adjusting for chronological age (C-age) and other covariables. Average C-age of the sample was 68.4 (±11.8) and we observed a relatively …

The Role Of Er Stress In Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome, Shuntaro Morikawa, Fumihiko Urano

2020-Current year OA Pubs

The endoplasmic reticulum (ER) is a cytosolic organelle that plays an essential role in the folding and processing of new secretory proteins, including insulin. The pathogenesis of diabetes, a group of metabolic disorders caused by dysfunctional insulin secretion (Type 1 diabetes, T1DM) or insulin sensitivity (Type 2 diabetes, T2DM), is known to involve the excess accumulation of "poorly folded proteins", namely, the induction of pathogenic ER stress in pancreatic β-cells. ER stress is known to contribute to the dysfunction of the insulin-producing pancreatic β-cells. T1DM and T2DM are multifactorial diseases, especially T2DM; both environmental and genetic factors are involved in …

In Silico Activity And Admet Profiling Of Phytochemicals From Ethiopian Indigenous Aloes Using Pharmacophore Models, Lemessa Etana Bultum, Gemechu Bekele Tolossa, Gwangmin Kim, Ohhyeon Kwon, Doheon Lee

2020-Current year OA Pubs

In silico profiling is used in identification of active compounds and guide rational use of traditional medicines. Previous studies on Ethiopian indigenous aloes focused on documentation of phytochemical compositions and traditional uses. In this study, ADMET and drug-likeness properties of phytochemicals from Ethiopian indigenous aloes were evaluated, and pharmacophore-based profiling was done using Discovery Studio to predict therapeutic targets. The targets were examined using KEGG pathway, gene ontology and network analysis. Using random-walk with restart algorithm, network propagation was performed in CODA network to find diseases associated with the targets. As a result, 82 human targets were predicted and found …

Trem2 Dependent And Independent Functions Of Microglia In Alzheimer's Disease, Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna

2020-Current year OA Pubs

Microglia are central players in brain innate immunity and have been the subject of extensive research in Alzheimer's disease (AD). In this review, we aim to summarize the genetic and functional discoveries that have advanced our understanding of microglia reactivity to AD pathology. Given the heightened AD risk posed by rare variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2), we will focus on the studies addressing the impact of this receptor on microglia responses to amyloid plaques, tauopathy and demyelination pathologies in mouse and human. Finally, we will discuss the implications of recent discoveries on microglia …

Associations Between Mental Health And Hiv Status Among Sexual Minority And Heterosexual Adolescents In Nigeria, Morenike Oluwatoyin Folayan, Olakunle Oginni, Olanrewaju Ibikunle Ibigbami, Uma Philip, Nserd Ntonoba Mfam, Chinedu Mbam, Amos Ganyam, Agada A Salem, Christopher Osuji, Cory Bradley, Joanne Lusher, Nadia Adjoa Sam-Agudu

2020-Current year OA Pubs

BACKGROUND: We aimed to determine associations between the mental health status of adolescents by self-reported sexual identity; and to determine associations between the mental health status of sexual minority adolescents living with and without HIV.

METHODS: This cross-sectional study collected data from Nigerians aged 13-19 years old using an online survey. We collected information on dependent (sexual identity) and independent (presence of depressive symptoms, generalised anxiety disorder, suicidal attempt/ideation, HIV status) study variables. A multivariate regression model determined associations between the dependent and independent variables. A second multivariate regression model was developed to establish associations between HIV status among sexual …

Stakeholder Perspectives On The Demand And Supply Factors Driving Substandard And Falsified Blood Pressure Lowering Medications In Nigeria: A Qualitative Study, Grace Shedul, Olutobi Adekunle Sanuade, Eugenia N Ugwuneji, Tunde M Ojo, Aishwarya Vijay, Patrick Ponzing, Inuwa Okpe, Gabriel Lamkur Shedul, Mark D Huffman, Dike Ojji, Lisa R Hirschhorn

2020-Current year OA Pubs

OBJECTIVES: Although substandard and falsified (SF) blood pressure (BP) lowering medications are a global problem, qualitative research exploring factors driving this in Nigeria has not been reported. This study provides information on factors driving demand for and supply of low-quality BP lowering medications in Nigeria and potential strategies to address these factors.

METHODS: This was a cross-sectional qualitative study. Between August 2020 and September 2020, we conducted 11 in-depth interviews and 7 focus group discussions with administrators of health facilities, major manufacturers and distributors of BP lowering medications, pharmacists, drug regulators, patients and primary care physicians purposively sampled from the …

Myocardial Contractility Pattern Characterization In Radiation-Induced Cardiotoxicity Using Magnetic Resonance Imaging: A Pilot Study With Contractix, El-Sayed H Ibrahim, Antonio Sosa, Sherry-Ann Brown, Dayeong An, Slade Klawikowski, John Baker, Carmen Bergom

2020-Current year OA Pubs

Radiation therapy (RT) plays an integral role in treating thoracic cancers, despite the risk of radiation-induced cardiotoxicity. We hypothesize that our newly developed magnetic resonance imaging (MRI)-based contractility index (ContractiX) is a sensitive marker for early detection of RT-induced cardiotoxicity in a preclinical rat model of thoracic cancer RT. Adult salt-sensitive rats received image-guided heart RT and were imaged with MRI at 8 weeks and 10 weeks post-RT or sham. The MRI exam included cine and tagging sequences to measure left-ventricular ejection fraction (LVEF), mass, myocardial strain, and ContractiX. Furthermore, ventricular torsion, diastolic strain rate, and mechanical dyssynchrony were measured. …

Effectiveness Of Soluble Ctla-4-Fc In The Inhibition Of Bone Marrow T-Cell Activation In Context Of Indoleamine 2.3-Dioxygenase (Ido) And Cd4+Foxp3+ Treg Induction, Magdalena Massalska, Marzena Ciechomska, Ewa Kuca-Warnawin, Tomasz Burakowski, Anna Kornatka, Anna Radzikowska, Dariusz Pawlak, Barbara Muz, Adrianna Loniewska-Lwowska, Andrzej Palucha, Pawel Maldyk, Wlodzimierz Maslinski

2020-Current year OA Pubs

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease with systemic inflammation finally resulting in damaged joints. One of the RA development models suggests bone marrow (BM) as a place of inflammation development further leading to disease progression. We aimed to investigate the potential of CTLA-4-Fc molecule in inducing tolerogenic milieu in BM measured as indoleamine 2,3-dioxygenase (IDO) expression, CD4

METHODS: Bone marrow mononuclear cells (BMMC) were stimulated by pro-inflammatory cytokines and CTLA-4-Fc. Next IDO expression, CD4

RESULTS: We found that CTLA-4-Fc and IFN-γ stimulation results in IDO production by BMMC. CTLA-4-Fc induced tryptophan catabolism can inhibit mitogen-induced CD4

CONCLUSION: …

Advice To Clinicians On Communication From Adolescents And Young Adults With Cancer And Parents Of Children With Cancer, Meghana Srinivas, Erica C Kaye, Lindsay J Blazin, Justin N Baker, Jennifer W Mack, James M Dubois, Bryan A Sisk

2020-Current year OA Pubs

Effective communication is integral to patient and family-centered care in pediatric and adolescent and young adult (AYA) oncology and improving healthcare delivery and outcomes. There is limited knowledge about whether AYAs and parents have similar communication preferences and needs. By eliciting and comparing communication advice from AYAs and parents, we can identify salient guidance for how clinicians can better communicate. We performed secondary analysis of semi-structured interviews from 2 qualitative communication studies. In one study, 80 parents of children with cancer during treatment, survivorship, or bereavement were interviewed. In the second study, AYAs with cancer during treatment or survivorship were …

Sodium Content And Labelling Of Packaged Foods And Beverages In Nigeria: A Cross-Sectional Study, Adedayo E Ojo, Mark D Huffman, Et Al.

2020-Current year OA Pubs

Increased consumption of unhealthy processed foods, particularly those high in sodium, is a major risk factor for cardiovascular diseases. The nutrition information on packaged foods can help guide consumers toward products with less sodium and support government actions to improve the healthiness of the food supply. The aims of this study were to estimate the proportion of packaged foods displaying nutrition information for sodium and other nutrients specified by Nigerian nutrition labelling regulations and to determine the amount of sodium in packaged foods sold in Nigeria using data from the nutritional information panel. Data were collected from November 2020 to …

Utilization Of Cardiovascular Magnetic Resonance (Cmr) Imaging For Resumption Of Athletic Activities Following Covid-19 Infection: An Expert Consensus Document On Behalf Of The American Heart Association Council On Cardiovascular Radiology And Intervention (Cvri) Leadership And Endorsed By The Society For Cardiovascular Magnetic Resonance (Scmr), Frederick L. Ruberg, Aaron L. Baggish, Allison G. Hays, Michael Jerosch-Herold, Jiwon Kim, Karen G. Ordovas, Gautham Reddy, Chetan Shenoy, Jonathan W. Weinsaft, Pamela K. Woodard

2020-Current year OA Pubs

The global pandemic of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory suyndrome coronavirus 2 (SARS-CoV-2) is now entering its 4th year with little evidence of abatement. As of December 2022, the World Health Organization Coronavirus (COVID-19) Dashboard reported 643 million cumulative confirmed cases of COVID-19 worldwide and 98 million in the United States alone as the country with the highest number of cases. While pneumonia with lung injury has been the manifestation of COVID-19 principally responsible for morbidity and mortality, myocardial inflammation and systolic dysfunction though uncommon are well-recognized features that also associate with adverse prognosis. …

Expanded Proteomic Survey Of The Human Parasite Leishmania Major Focusing On Changes In Null Mutants Of The Golgi Gdp-Mannose/Fucose/Arabinopyranose Transporter, Gloria Polanco, Nichollas E Scott, Lon F Lye, Stephen M Beverley

2020-Current year OA Pubs

The trypanosomatid protozoan parasite

A Mobile Phone Text Messaging Intervention To Manage Fatigue For People With Multiple Sclerosis, Spinal Cord Injury, And Stroke: Development And Usability Testing, Kerri A. Morgan, Alex W K Wong, Kim Walker, Rachel Heeb Desai, Tina M Knepper, Pamela K Newland

2020-Current year OA Pubs

BACKGROUND: Fatigue significantly affects daily functioning in persons with disabilities. Fatigue management can be challenging, and the information provided during routine physician visits to manage fatigue can be overwhelming. One way to address fatigue is to increase knowledge, skills, and confidence for self-management (ie, patient activation). Self-management programs have shown promising effects in targeting fatigue in persons with disabilities. However, satisfaction with self-management programs is low for persons with disabilities, and tailoring interventions to personalized needs has been recommended. SMS text messaging is increasingly being used to implement health behavior change interventions in a person's natural environment. Little has been …

Impact Of Cd4 T Cells On Intratumoral Cd8 T-Cell Exhaustion And Responsiveness To Pd-1 Blockade Therapy In Mouse Brain Tumors, Saad M. Khan, Rupen Desai, Andrew Coxon, Alexandra Livingstone, Gavin P Dunn, Allegra Petti, Tanner M Johanns

2020-Current year OA Pubs

BACKGROUND: Glioblastoma is a fatal disease despite aggressive multimodal therapy. PD-1 blockade, a therapy that reinvigorates hypofunctional exhausted CD8 T cells (T

METHODS: Single-cell RNA sequencing was performed on flow sorted tumor-infiltrating lymphocytes from female C57/BL6 mice implanted with each model, with and without PD-1 blockade therapy. CD8

RESULTS: The CD8 T-cell compartment of the models is composed of heterogenous CD8 T

CONCLUSIONS: Here, we describe that dysfunctional CD4 T cells are associated with terminal CD8 T-cell exhaustion, suggesting CD4 T cells impact PD-1 blockade efficacy by controlling the severity of exhaustion. Given that CD4 lymphopenia is frequently observed in …

Lecanemab In Patients With Early Alzheimer's Disease: Detailed Results On Biomarker, Cognitive, And Clinical Effects From The Randomized And Open-Label Extension Of The Phase 2 Proof-Of-Concept Study, Eric Mcdade, Jeffrey L Cummings, Shobha Dhadda, Chad J Swanson, Larisa Reyderman, Michio Kanekiyo, Akihiko Koyama, Michael Irizarry, Lynn D Kramer, Randall J Bateman

2020-Current year OA Pubs

BACKGROUND: Lecanemab, a humanized IgG1 monoclonal antibody that targets soluble aggregated Aβ species (protofibrils), has demonstrated robust brain fibrillar amyloid reduction and slowing of clinical decline in early AD. The objective of this analysis is to report results from study 201 blinded period (core), the open-label extension (OLE), and gap period (between core and OLE) supporting the effectiveness of lecanemab.

METHODS: The lecanemab study 201 core was a double-blind, randomized, placebo-controlled study of 856 patients randomized to one of five dose regimens or placebo. An OLE of study 201 was initiated to allow patients to receive open-label lecanemab 10mg/kg biweekly …

Utilization Of Cardiovascular Magnetic Resonance (Cmr) Imaging For Resumption Of Athletic Activities Following Covid-19 Infection: An Expert Consensus Document On Behalf Of The American Heart Association Council On Cardiovascular Radiology And Intervention (Cvri) Leadership And Endorsed By The Society For Cardiovascular Magnetic Resonance (Scmr), Frederick L Ruberg, Aaron L Baggish, Allison G Hays, Michael Jerosch-Herold, Jiwon Kim, Karen G Ordovas, Gautham Reddy, Chetan Shenoy, Jonathan W Weinsaft, Pamela K Woodard

2020-Current year OA Pubs

The global pandemic of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory suyndrome coronavirus 2 (SARS-CoV-2) is now entering its 4th year with little evidence of abatement. As of December 2022, the World Health Organization Coronavirus (COVID-19) Dashboard reported 643 million cumulative confirmed cases of COVID-19 worldwide and 98 million in the United States alone as the country with the highest number of cases. While pneumonia with lung injury has been the manifestation of COVID-19 principally responsible for morbidity and mortality, myocardial inflammation and systolic dysfunction though uncommon are well-recognized features that also associate with adverse prognosis. …

A Genome-Wide Association Study Of 2304 Extreme Longevity Cases Identifies Novel Longevity Variants, Harold Bae, Ping An, Mary Feitosa, Et Al.

2020-Current year OA Pubs

We performed a genome-wide association study (GWAS) of human extreme longevity (EL), defined as surviving past the 99th survival percentile, by aggregating data from four centenarian studies. The combined data included 2304 EL cases and 5879 controls. The analysis identified a locus in CDKN2B-AS1 (rs6475609,

Antibodies Targeting The Neuraminidase Active Site Inhibit Influenza H3n2 Viruses With An S245n Glycosylation Site, Daniel Stadlbauer, Ali H Ellebedy, Et Al.

2020-Current year OA Pubs

Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.

Perspectives On Joint Eanm/Snmmi/Anzsnm Practice Guidelines/Procedure Standards For [18f]Fdg Pet/Ct Imaging During Immunomodulatory Treatments In Patients With Solid Tumors, E Lopci, R L Wahl, Et Al.

2020-Current year OA Pubs

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [

Self-Hybridization In Leishmania Major, Tiago R Ferreira, Ehud Inbar, Jahangheer Shaik, Brendan M Jeffrey, Kashinath Ghosh, Deborah E. Dobson, Stephen M. Beverley, David Sacks

2020-Current year OA Pubs

Genetic exchange between different

Morphologic Design Of Nanostructures For Enhanced Antimicrobial Activity, Fatma Al-Zahraa Sayed, Noura G Eissa, Yidan Shen, David A Hunstad, Karen L Wooley, Mahmoud Elsabahy

2020-Current year OA Pubs

Despite significant progress in synthetic polymer chemistry and in control over tuning the structures and morphologies of nanoparticles, studies on morphologic design of nanomaterials for the purpose of optimizing antimicrobial activity have yielded mixed results. When designing antimicrobial materials, it is important to consider two distinctly different modes and mechanisms of activity-those that involve direct interactions with bacterial cells, and those that promote the entry of nanomaterials into infected host cells to gain access to intracellular pathogens. Antibacterial activity of nanoparticles may involve direct interactions with organisms and/or release of antibacterial cargo, and these activities depend on attractive interactions and …

Cardiac Physical Exam Skills And Auscultation Session For Pediatric Interns, Christopher A Sumski, Anoop Singh, Amanda Rogers, Robert Treat, Charles Bergstrom

2020-Current year OA Pubs

INTRODUCTION: Physicians need adequate physical exam skills. Unfortunately, interns have variable physical exam skills, and teaching is often limited to rounds, an inconsistent setting. Physical exam skills, particularly those involving auscultation, require practice. Our goal was to create a cardiac physical exam workshop for pediatric interns that would improve their performance on an interactive assessment of their ability and understanding in physical exam and murmur interpretation.

METHODS: We completed a targeted needs assessment and then developed a 2-hour workshop on the pediatric cardiac physical exam targeted to pediatrics residents. The workshop included didactics, group discussion, and practice interpreting common pediatric …

A Unique High-Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance In Cantu Syndrome, Gautam K Singh, Conor Mcclenaghan, Manish Aggarwal, Hongjie Gu, Maria S Remedi, Dorothy K Grange, Colin G Nichols

2020-Current year OA Pubs

Background Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high-output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities. Methods and Results We sought to systematically characterize high-output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain-of-function variants in

Quality Assessment And Refinement Of Chromatin Accessibility Data Using A Sequence-Based Predictive Model, Seong Kyu Han, Yoshiharu Muto, Parker C Wilson, Benjamin D Humphreys, Matthew G Sampson, Aravinda Chakravarti, Dongwon Lee

2020-Current year OA Pubs

Chromatin accessibility assays are central to the genome-wide identification of gene regulatory elements associated with transcriptional regulation. However, the data have highly variable quality arising from several biological and technical factors. To surmount this problem, we developed a sequence-based machine learning method to evaluate and refine chromatin accessibility data. Our framework, gapped k-mer SVM quality check (gkmQC), provides the quality metrics for a sample based on the prediction accuracy of the trained models. We tested 886 DNase-seq samples from the ENCODE/Roadmap projects to demonstrate that gkmQC can effectively identify "high-quality" (HQ) samples with low conventional quality scores owing to marginal …

Type Iv Pili Are A Critical Virulence Factor In Clinical Isolates Of Paenibacillus Thiaminolyticus, Christine Hehnly, Petra Erdmann Gilmore, R. Reid Townsend, David D. Limbrick, Et Al.

2020-Current year OA Pubs

Hydrocephalus, the leading indication for childhood neurosurgery worldwide, is particularly prevalent in low- and middle-income countries. Hydrocephalus preceded by an infection, or postinfectious hydrocephalus, accounts for up to 60% of hydrocephalus in these areas. Since many children with hydrocephalus suffer poor long-term outcomes despite surgical intervention, prevention of hydrocephalus remains paramount. Our previous studies implicated a novel bacterial pathogen, Paenibacillus thiaminolyticus, as a causal agent of neonatal sepsis and postinfectious hydrocephalus in Uganda. Here, we report the isolation of three

Restoring Mitochondrial Cardiolipin Homeostasis Reduces Cell Death And Promotes Recovery After Spinal Cord Injury, Nai-Kui Liu, Chunyan Wang, Et Al.

2020-Current year OA Pubs

Alterations in phospholipids have long been associated with spinal cord injury (SCI). However, their specific roles and signaling cascades in mediating cell death and tissue repair remain unclear. Here we investigated whether alterations of cardiolipin (CL), a family of mitochondrion-specific phospholipids, play a crucial role in mitochondrial dysfunction and neuronal death following SCI. Lipidomic analysis was used to determine the profile of CL alteration in the adult rat spinal cord following a moderate contusive SCI at the 10th thoracic (T10) level. Cellular, molecular, and genetic assessments were performed to determine whether CL alterations mediate mitochondrial dysfunction and neuronal death after …

Caregiver Perceptions Of Change In Pediatric Asthma Control During The Covid-19 Pandemic, Gabrielle Pogge, Erika A Waters, Gregory D Webster, Sreekala Prabhakaran, Jean M Hunleth, David A Fedele, James A Shepperd

2020-Current year OA Pubs

PURPOSE: Although several indicators suggest that pediatric asthma control in the United States improved early in the pandemic, other indicators suggest not. Missing are reports from caregivers of the experiences of their children with asthma early in the pandemic.

METHODS: Using the PP-ACT and other measures that we specifically constructed for our research, we conducted a cross-sectional national survey of US caregivers of children with asthma (N=595) to examine perceived change in their child's asthma control and changes in reports of ED visits and use of emergency relief medicine and controller medicine pre-pandemic (January to March 2020) versus early-pandemic (June …

An Isochroman Analog Of Cd3254 And Allyl-, Isochroman-Analogs Of Net-Tmn Prove To Be More Potent Retinoid-X-Receptor (Rxr) Selective Agonists Than Bexarotene, Peter W Jurutka, Orsola Di Martino, Et Al.

2020-Current year OA Pubs

Bexarotene is an FDA-approved drug for the treatment of cutaneous T-cell lymphoma (CTCL); however, its use provokes or disrupts other retinoid-X-receptor (RXR)-dependent nuclear receptor pathways and thereby incites side effects including hypothyroidism and raised triglycerides. Two novel bexarotene analogs, as well as three unique CD3254 analogs and thirteen novel NEt-TMN analogs, were synthesized and characterized for their ability to induce RXR agonism in comparison to bexarotene (

Covid-19 Induces Cns Cytokine Expression And Loss Of Hippocampal Neurogenesis, Allison L Soung, Abigail Vanderheiden, Xiaoping Jiang, Traci Bricker, Adrianus C M Boon, Robyn S Klein, Et Al.

2020-Current year OA Pubs

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied. Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1β and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the …

A Whole-Genome Sequencing Study Implicates Gramd1b In Multiple Sclerosis Susceptibility, Federica Esposito, Bryan Bollman, Laura Piccio, Et Al.

2020-Current year OA Pubs

While the role of common genetic variants in multiple sclerosis (MS) has been elucidated in large genome-wide association studies, the contribution of rare variants to the disease remains unclear. Herein, a whole-genome sequencing study in four affected and four healthy relatives of a consanguineous Italian family identified a novel missense c.1801T > C (p.S601P) variant in the