Low frequency of the PARK2 gene mutations in Polish patients with the early-onset form of Parkinson disease

2010 ◽  
Vol 16 (2) ◽  
pp. 136-138 ◽  
Author(s):  
Dariusz Koziorowski ◽  
Dorota Hoffman-Zacharska ◽  
Jarosław Sławek ◽  
Walentyna Szirkowiec ◽  
Piotr Janik ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Early Onset ◽  
Low Frequency ◽  
Gene Mutations

scholarly journals Mutation spectrum of NOD2 reveals recessive inheritance as a main driver of Early Onset Crohn’s Disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julie E. Horowitz ◽  
Neil Warner ◽  
Jeffrey Staples ◽  
Eileen Crowley ◽  
Nehal Gosalia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Protein Function ◽  
Early Onset ◽  
Low Frequency ◽  
Mendelian Inheritance ◽  
Clinical Population ◽  
Mendelian Disease ◽  
Recessive Inheritance ◽  
Pediatric Onset

AbstractInflammatory bowel disease (IBD), clinically defined as Crohn’s disease (CD), ulcerative colitis (UC), or IBD-unclassified, results in chronic inflammation of the gastrointestinal tract in genetically susceptible hosts. Pediatric onset IBD represents ≥ 25% of all IBD diagnoses and often presents with intestinal stricturing, perianal disease, and failed response to conventional treatments. NOD2 was the first and is the most replicated locus associated with adult IBD, to date. However, its role in pediatric onset IBD is not well understood. We performed whole-exome sequencing on a cohort of 1,183 patients with pediatric onset IBD (ages 0–18.5 years). We identified 92 probands with biallelic rare and low frequency NOD2 variants accounting for approximately 8% of our cohort, suggesting a Mendelian inheritance pattern of disease. Additionally, we investigated the contribution of recessive inheritance of NOD2 alleles in adult IBD patients from a large clinical population cohort. We found that recessive inheritance of NOD2 variants explains ~ 7% of cases in this adult IBD cohort, including ~ 10% of CD cases, confirming the observations from our pediatric IBD cohort. Exploration of EHR data showed that several of these adult IBD patients obtained their initial IBD diagnosis before 18 years of age, consistent with early onset disease. While it has been previously reported that carriers of more than one NOD2 risk alleles have increased susceptibility to Crohn’s Disease (CD), our data formally demonstrate that recessive inheritance of NOD2 alleles is a mechanistic driver of early onset IBD, specifically CD, likely due to loss of NOD2 protein function. Collectively, our findings show that recessive inheritance of rare and low frequency deleterious NOD2 variants account for 7–10% of CD cases and implicate NOD2 as a Mendelian disease gene for early onset Crohn’s Disease.

Reduced event-related low frequency EEG activity in patients with early onset schizophrenia and their unaffected siblings

2015 ◽  
Vol 232 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Molly Simmonite ◽  
Alan Thomas Bates ◽  
Madeleine Groom ◽  
Chris Hollis ◽  
Peter Francis Liddle
Keyword(s):  
Early Onset ◽  
Low Frequency ◽  
Early Onset Schizophrenia ◽  
Eeg Activity

scholarly journals Whole-exome sequencing associates novel CSMD1 gene mutations with familial Parkinson disease

2017 ◽  
Vol 3 (5) ◽  
pp. e177 ◽  
Author(s):  
Javier Ruiz-Martínez ◽  
Luis J. Azcona ◽  
Alberto Bergareche ◽  
Jose F. Martí-Massó ◽  
Coro Paisán-Ruiz
Keyword(s):  
Parkinson Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genome Wide Association Study ◽  
Single Gene ◽  
Gene Mutations ◽  
Complement Control Protein ◽  
Genome Wide ◽  
Whole Exome ◽  
A Genome

Objective:Despite the enormous advancements made in deciphering the genetic architecture of Parkinson disease (PD), the majority of PD is idiopathic, with single gene mutations explaining only a small proportion of the cases.Methods:In this study, we clinically evaluated 2 unrelated Spanish families diagnosed with PD, in which known PD genes were previously excluded, and performed whole-exome sequencing analyses in affected individuals for disease gene identification.Results:Patients were diagnosed with typical PD without relevant distinctive symptoms. Two different novel mutations were identified in the CSMD1 gene. The CSMD1 gene, which encodes a complement control protein that is known to participate in the complement activation and inflammation in the developing CNS, was previously shown to be associated with the risk of PD in a genome-wide association study.Conclusions:We conclude that the CSMD1 mutations identified in this study might be responsible for the PD phenotype observed in our examined patients. This, along with previous reported studies, may suggest the complement pathway as an important therapeutic target for PD and other neurodegenerative diseases.

scholarly journals Early-onset vs. Late-onset Parkinson’s disease: A Clinical-pathological Study

2015 ◽  
Vol 43 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Leslie Wayne Ferguson ◽  
Ali H. Rajput ◽  
Alexander Rajput
Keyword(s):  
Parkinson Disease ◽  
Early Onset ◽  
Disease Duration ◽  
Late Onset ◽  
Disease Onset ◽  
Clinic Visit ◽  
Pathological Study ◽  
Younger Age ◽  
Wearing Off ◽  
Selection For

AbstractBackground:Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases.Methods:We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases.Results:At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed in EOPD. Lifetime use of amantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD.Conclusions:Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD.

scholarly journals Early-Onset Parkinson Disease Screening in Patients From Nigeria

2021 ◽  
Vol 11 ◽  
Author(s):  
Lukasz M. Milanowski ◽  
Olajumoke Oshinaike ◽  
Benjamin J. Broadway ◽  
Jennifer A. Lindemann ◽  
Alexandra I. Soto-Beasley ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Parkinson Disease ◽  
Neurodegenerative Diseases ◽  
Early Onset ◽  
Local Population ◽  
Age At Onset ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
African Countries ◽  
Age Related

Introduction: 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 PRKN, PINK1, DJ1, SNCA multiplication, and LRRK2 p.G2019S.Methods: We assembled a cohort of 109 Nigerian patients with PD from the four main Nigerian tribes: Yoruba, Igbo, Edo, and Hausa. Fifteen cases [14 from the Yoruba tribe (93.3%)] had EOPD (defined as age-at-onset &lt;50 years). All patients with EOPD were sequenced for the coding regions of PRKN, PINK1, and DJ1. Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a SNCA probe and LRRK2 p.G2019S. We screened for LRRK2 p.G2019S in the entire PD cohort using a genotyping assay. The PINK1 p.R501Q functional analysis was conducted.Results: In 15 patients with EOPD, 22 variants were observed [PRKN, 9 (40.9%); PINK1, 10 (45.5%); and DJ1, 3 (13.6%)]. Three (13.6%) rare, nonsynonymous variants were identified, but no homozygous or compound heterozygous carriers were found. No exonic rearrangements were present in the three genes, and no carriers of SNCA genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function.Conclusion: More studies on age-related neurodegenerative diseases are needed in sub-Saharan African countries, including Nigeria. Population-specific variation may provide insight into the genes involved in PD in the local population but may also contribute to larger studiesperformed in White and Asian populations.

3.023 FREQUENCY OF THE MUTATIONS IN THE PARK2, PINK1 AND DJ-1 GENES IN POLISH PATIENTS WITH THE EARLY-ONSET PARKINSON DISEASE

2012 ◽  
Vol 18 ◽  
pp. S174-S175
Author(s):  
D. Koziorowski ◽  
D. Hoffman-Zacharska ◽  
J. Sławek ◽  
P. Górka ◽  
J. Bal ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Early Onset

scholarly journals Motor Phenotype of LRRK2 G2019S Carriers in Early-Onset Parkinson Disease

2009 ◽  
Vol 66 (12) ◽  
Author(s):  
Roy N. Alcalay ◽  
Helen Mejia-Santana ◽  
Ming Xin Tang ◽  
Llency Rosado ◽  
Miguel Verbitsky ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Early Onset ◽  
Lrrk2 G2019s ◽  
Motor Phenotype

scholarly journals Aggrecanopathies highlight the need for genetic evaluation of ISS children

2020 ◽  
Vol 183 (2) ◽  
pp. C9-C10
Author(s):  
Ola Nilsson
Keyword(s):  
Short Stature ◽  
Osteochondritis Dissecans ◽  
Early Onset ◽  
Gene Mutations ◽  
Bone Age ◽  
Genetic Evaluation ◽  
Large Cohort ◽  
Growth Disorders ◽  
Common Causes ◽  
Work Up

Short stature is one of the most common causes for referrals to pediatric endocrinologists. However, in a majority of the children, no underlying cause can be identified and the child instead receives the unhelpful diagnosis of idiopathic short stature (ISS), often after extensive work-up and testing. Recent advances in genetic methodology have allowed for the identification of a number of different monogenic conditions within the large cohort of ISS children. Isolated short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (MIM#165800) due to heterozygous aggrecan gene mutations exemplifies how this progress is changing the way we assess, counsel and treat children with non-endocrine growth disorders.

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