Multi-tracer PET correlation analysis reveals disease-specific patterns in Parkinson's disease and asymptomatic LRRK2 pathogenic variant carriers compared to healthy controls.

Several genetic pathogenic variants increase the risk of Parkinson's disease (PD) with pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene being among the most common. A joint pattern analysis based on multi-set canonical correlation analysis (MCCA) was utilized to extract PD and LRRK2 pathogenic variant-specific spatial patterns in relation to healthy controls (HCs) from multi-tracer Positron Emission Tomography (PET) data. Spatial patterns were extracted for individual subject cohorts, as well as for pooled subject cohorts, to explore whether complementary spatial patterns of dopaminergic denervation are different in the asymptomatic and symptomatic stages of PD.

Perry syndrome: Novel DCTN1 mutation in a large kindred and first observation of prodromal disease.

Introduction: Perry syndrome (PS) is a hereditary neurodegenerative disorder caused by mutations in the DCTN1 gene and characterized by TDP-43 pathology. As the diagnosis is usually made at the advanced stages of the disease, there are no studies on the asymptomatic mutation carriers and their conversion to overt disease.

Methods: We personally examined 27 members of the large kindred of 104 individuals with familial parkinsonism.

Neuropsychological profile of CSF1R-related leukoencephalopathy.

Introduction: The neuropsychological profile of CSF1R-related leukoencephalopathy (CRL) is undefined. This study defines the profile, contrasts it with that of other dementia syndromes, and highlights measures sensitive to cognitive impairment.

Methods: We administered a standardized battery of neuropsychological tests to five consecutive CRL cases.

Expanding the spectrum of mutations-case report of a large kindred with familial ALS and overlapping syndrome.

Objectives: This paper presents the first report of amyotrophic lateral sclerosis (ALS) kindred due to the p.Arg1007Lys, a splice-altering variant.

Methods: An index case was a 54-year-old male who developed progressive gait difficulty and imbalance followed by mild parkinsonism, spasticity, neuropathy, ataxia, and cognitive impairment with predominant subcortical frontal involvement.

Cathepsin B p.Gly284Val Variant in Parkinson's Disease Pathogenesis.

Parkinson's disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings.

Clinical, pathological and genetic characteristics of Perry disease-new cases and literature review.

Background And Purpose: Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease.

Early-Onset Parkinson Disease Screening in Patients From Nigeria.

Nigeria is one of the most populated countries in the world; however, there is a scarcity of studies in patients with age-related neurodegenerative diseases, such as Parkinson disease (PD). The aim of this study was to screen patients with PD including a small cohort of early-onset PD (EOPD) cases from Nigeria for multiplication, and LRRK2 p.G2019S.

Spinocerebellar ataxia type 6 family with phenotypic overlap with Multiple System Atrophy.

Aim Of The Study: Multiple system atrophy (MSA) and spinocerebellar ataxia (SCA) share similar symptomatology. We describe a rare occurrence of familial MSA that proved to be SCA6 upon genetic analysis.

Materials And Methods: Eighty MSA patients were enrolled in our study; blood samples were collected and genetic screening of the familial case for known SCA loci was performed.

Crohn's and Parkinson's Disease-Associated LRRK2 Mutations Alter Type II Interferon Responses in Human CD14 Blood Monocytes Ex Vivo.

The Leucine Rich Repeat Kinase 2 (LRRK2) is one of causative genes of familial Parkinson's disease (PD). The M2397T polymorphism in LRRK2 is genetically associated with sporadic Crohn's disease (CD). LRRK2 is expressed in human CD14 monocytes, induced by interferon-γ (IFN-γ) and suppresses inflammatory activation.

TRIO gene segregation in a family with cerebellar ataxia.

Aim Of The Study: To report a family with a novel TRIO gene mutation associated with phenotype of cerebellar ataxia.

Materials And Methods: Seven family members of Caribbean descent were recruited through our ataxia research protocol; of the family members, the mother and all 3 children were found to be affected with severe young-onset and rapidly progressive truncal and appendicular ataxia leading to early disability. Array comparative genomic hybridization, mitochondrial DNA analysis, and whole-exome sequencing were performed on 3 of the family members (mother and 2 daughters).

Comparison of clinical features among Parkinson's disease subtypes: A large retrospective study in a single center.

Introduction: Tremor dominant (TD), postural instability/gait difficulty (PIGD), and akinetic-rigid (AR) subtypes are widely used in classifying patients with Parkinson's disease (PD).

Methods: We compared clinical characteristics between PD subtypes in a large retrospective cohort. Between 1998 and 2016, we included a total of 1003 patients with PD in this retrospective study.

Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies.

Background: People with Parkinson's disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson's disease and individuals with sporadic Parkinson's disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes.

Methods: We did two cross-sectional PET studies at the Pacific Parkinson's Research Centre in Vancouver, BC, Canada.

Occurrence of Crohn's disease with Parkinson's disease.

We retrospectively investigated the co-occurrence of Crohn's disease in a cohort of 876 patients with Parkinson's disease, based on the observation that LRRK2 is a shared genetic risk factor. We identified 2 patients with Crohn's disease; this number was consistent with the number of cases expected in the general population.

Spinocerebellar ataxia 15: A phenotypic review and expansion.

Spinocerebellar ataxia 15 (SCA15) is a clinically heterogeneous movement disorder characterized by the adult onset of slowly progressive cerebellar ataxia. ITPR1 is the SCA15 causative gene. However, despite numerous reports of genetically-confirmed SCA15, phenotypic uncertainty persists.

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms.

RAB39B gene mutations are not a common cause of Parkinson's disease or dementia with Lewy bodies.

Mutations in Ras-related protein Rab-39B (RAB39B) gene have been linked to X-linked early-onset Parkinsonism with intellectual disabilities. The aim of this study was to address the genetic contribution of RAB39B to Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pathologically confirmed Lewy body dementia (pLBD) cases. A cohort of 884 PD, 399 DLB, and 379 pLBD patients were screened for RAB39B mutations, but no coding variants were found, suggesting RAB39B mutations are not a common cause of PD, DLB, or pLBD in Caucasian population.

Cancer in Parkinson's disease.

Introduction: We examined the prevalence of cancer in patients with Parkinson's disease (PD) and controls evaluated at the Mayo Clinic in Jacksonville, Florida, between 2003 and 2014.

Methods: We retrospectively collected information regarding cancer diagnoses and diagnosis of PD from 971 unrelated PD patients and 478 controls, and all were white. For PD patients, we examined cancers diagnosed before and after PD diagnosis separately in addition to considering all cancer diagnoses.

Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders.

Objective: To assess the role of CHCHD2 variants in patients with Parkinson disease (PD) and Lewy body disease (LBD) in Caucasian populations.

Methods: All exons of the CHCHD2 gene were sequenced in a US Caucasian patient-control series (878 PD, 610 LBD, and 717 controls). Subsequently, exons 1 and 2 were sequenced in an Irish series (355 PD and 365 controls) and a Polish series (394 PD and 350 controls).

Frontotemporal dementia-associated N279K tau mutant disrupts subcellular vesicle trafficking and induces cellular stress in iPSC-derived neural stem cells.

Background: Pallido-ponto-nigral degeneration (PPND), a major subtype of frontotemporal dementia with parkinsonism related to chromosome 17 (FTDP-17), is a progressive and terminal neurodegenerative disease caused by c.837 T > G mutation in the MAPT gene encoding microtubule-associated protein tau (rs63750756; N279K). This MAPT mutation induces alternative splicing of exon 10, resulting in a modification of microtubule-binding region of tau.

DNAJC13 p.Asn855Ser mutation screening in Parkinson's disease and pathologically confirmed Lewy body disease patients.

Background: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family.

Methods: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD).

A novel tau mutation, p.K317N, causes globular glial tauopathy.

Globular glial tauopathies (GGTs) are 4-repeat tauopathies neuropathologically characterized by tau-positive, globular glial inclusions, including both globular oligodendroglial inclusions and globular astrocytic inclusions. No mutations have been found in 25 of the 30 GGT cases reported in the literature who have been screened for mutations in microtubule associated protein tau (MAPT). In this report, six patients with GGT (four with subtype III and two with subtype I) were screened for MAPT mutations.

Whole-exome sequencing as a diagnostic tool in a family with episodic ataxia type 1.

Complex neurologic phenotypes are inherently difficult to diagnose. Whole-exome sequencing (WES) is a new tool in the neurologist's diagnostic armamentarium. Whole-exome sequencing can be applied to investigate the "diagnostic odyssey" cases.