Plasticity-related gene 3 (
            <i>LPPR1</i>
            ) and age at diagnosis of Parkinson disease

Wallen, Zachary D.; Chen, Honglei; Hill-Burns, Erin M.; Factor, Stewart A.; Zabetian, Cyrus P.; Payami, Haydeh

doi:10.1212/nxg.0000000000000271

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…In 2016, a further dataset, Eigen, was released, for which calculation was performed without training data but with a principal component that gives the largest diversity among the variants prepared from all possible single-nucleotide changes in the human genome [ 33 ]. These annotation tools have achieved some clinically significant findings in genome-wide association studies (for example, see [ 49 , 50 ]). Recently, The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium successfully applied CADD to estimate the biological impacts of cancer mutations [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2)

et al. 2021

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Identification of the population frequencies of definitely pathogenic germline variants in two major hereditary breast and ovarian cancer syndrome (HBOC) genes, BRCA1/2, is essential to estimate the number of HBOC patients. In addition, the identification of moderately penetrant HBOC gene variants that contribute to increasing the risk of breast and ovarian cancers in a population is critical to establish personalized health care. A prospective cohort subjected to genome analysis can provide both sets of information. Computational scoring and prospective cohort studies may help to identify such likely pathogenic variants in the general population. We annotated the variants in the BRCA1 and BRCA2 genes from a dataset of 3,552 whole-genome sequences obtained from members of a prospective cohorts with genome data in the Tohoku Medical Megabank Project (TMM) with InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAFs) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar were used for filtration criteria. Familial predispositions to cancers among the 35,000 TMM genome cohort participants were analyzed to verify the identified pathogenicity. Seven potentially pathogenic variants were newly identified. The sisters of carriers of these moderately deleterious variants and definite P and LP variants among members of the TMM prospective cohort showed a statistically significant preponderance for cancer onset, from the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potentially pathogenic variants in BRCA genes in the Japanese population. These results should help to follow up the carriers of variants of uncertain significance in the HBOC genes in the longitudinal prospective cohort study.

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Section: Resultsmentioning

confidence: 99%

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2)

et al. 2021

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show abstract

“…In 2016, a further dataset, Eigen, was released, for which calculation was performed without training data but with a principal component that gives the largest diversity among the variants prepared from all possible single-nucleotide changes in the human genome [32]. These annotation tools show some clinically significant findings in genome-wide association studies (for examples, see [47, 48]). Recently, The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium applied CADD for their estimation of biological impacts of cancer mutations [49].…”

Section: Resultsmentioning

confidence: 99%

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes in a 3,552 Japanese whole-genome sequence dataset (3.5KJPNv2)

Tokunaga

Iida

Hozawa

et al. 2020

Preprint

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Identification of pathogenic germline variants yet no clinical evidence in BRCA genes has become important in patient care of hereditary breast and ovarian cancer syndrome (HBOC). Computational scoring and prospective cohort studies may help to identify such pathogenic variants. We annotated the variants in the BRCA1 and BRCA2 genes from a dataset of 3,552 whole-genome sequences obtained from members of the genome cohorts by Tohoku Medical Megabank Project (TMM) with the InterVar software. Computational impact scores (CADD_phred and Eigen_raw) and minor allele frequencies (MAF) of pathogenic (P) and likely pathogenic (LP) variants in ClinVar are used for filtration criteria. Familial predispositions in cancers among the 35,000 TMM genome cohort participants are analyzed to verify the pathogenicity. Seven potentially pathogenic variants were newly identified. Carriers of these potential pathogenic variants and definite P and LP variants among participants of the TMM prospective cohort show a statistically significant preponderance in cancer onset in sisters in the self-reported cancer history. Filtering by computational scoring and MAF is useful to identify potential pathogenic variants in BRCA genes for Japanese population. These results will be helpful to follow up the carriers of variants of uncertain significance in the HBOC genes.

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“…15 (b) We only selected several representative demographic and clinical items to evaluate subjects. 15 (b) We only selected several representative demographic and clinical items to evaluate subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous pathogenic genes and environmental threats were committed to the pathogenesis of PD, while no unified conclusion could explain the underlying cause. 15 It was believed that disruption of mitochondrial homeostasis and subsequent mitochondrial dysfunction would play a critical role in the development of neurodegenerative diseases including PD. 14,16 Generally, nerve cells clear damaged mitochondria through mitochondrial autophagy, thereby controlling the quality of the protein produced to maintain the normal function of the nerve cells.…”

Section: Discussionmentioning

confidence: 99%

MUL1 gene polymorphisms and Parkinson’s disease risk

Taximaimaiti

2019

Acta Neurol Scand

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| INTRODUC TI ONParkinson's disease (PD) is the second most common neurodegenerative disorder worldwide characterized by dopaminergic neuron loss in the substantia nigra. 1 PD expresses as some motor symptoms (MS) like tremors, slowness, rigidity, as well as some non-motor symptoms (NMS) include dementia, depression, constipation, et al 2,3 Although drugs can help to release the pain and movement disorder, PD cannot be cured or halted at present. 4 Recently, several genome-wide association studies (GWAs) have found some multiple risk loci for PD, which may pave a road to future gene therapy. 5,6 Mitochondrial ubiquitin ligase 1 (MUL1), also known as RNF218, C1orf166, growth inhibition and death E3 ligase (GIDE), mitochondrial-anchored protein ligase (MAPL), and mitochondrial ubiquitin ligase activator of NF-kB (MULAN), is an E3 protein ligase. 7 Well known to stabilize Drp1 and degrade Mfn, MUL1 expression results in smaller and more fragmented mitochondria, which is achieved by small ubiquitin-like modifier (SUMO) ligase activity and ubiquitin ligase activity, and can lead to apoptosis. 7,8 When over or under expressed, MUL1 can slow or accelerate cell growth, respectively, via pathways involving caspases activation and c-Jun N-terminal kinase (JNK) activation which can induce apoptosis. 9 Recent researches indicated that MUL1 may play a key role in PD pathogenesis. Jina Yun and his team found the MUL1 pathway could help maintain mitochondrial integrity by compensating for loss of PINK1/parkin and ameliorate PD motor symptoms in drosophila and mammals. 4,10 Another research in mice uncovered that suppression of MUL1 expression in VPS35-deficient DA neurons could restore PD-related defects, including mitochondrial fragmentation and DA neuronal loss. 11 These results certified that MUL1 may act as an individualized therapeutic gene target for PD treatment. Although many studies have been conducted to explore the structure and function of MUL1 in mitochondria, 8,9 there are few reports on the relationship between MUL1 genetic variations and PD pathogenesis, which is more clinically useful. With this in mind, we conducted a case-control study in a Chinese population to evaluate the possible association between single nucleotide polymorphisms (SNPs) in MUL1 gene and PD development.Objectives: Parkinson's disease (PD) is afflicting millions of patients worldwide, and gene therapy may be a hope for cure. Recent researches have shown that MUL1 may play a key role in PD pathogenesis, but no specific genetic variants have been identified. This study was aimed to verify the hypothesis that variants in MUL1 gene were associated with PD risk in a Chinese cohort.Methods: Ten single nucleotide polymorphisms of the MUL1 gene were genotyped through Sanger sequencing in a case-control study containing 100 PD patients and 100 controls matched for age and gender. Results: Our results showed that rs529974 in MUL1 gene was significantly associated with the risk of PD. The allele T in rs529974(+) caused an additional PD tendency (O...

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Plasticity-related gene 3 ( LPPR1 ) and age at diagnosis of Parkinson disease

Cited by 12 publications

References 34 publications

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2)

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes from a dataset of 3,552 Japanese whole genomes (3.5KJPNv2)

Novel candidates of pathogenic variants of the BRCA1 and BRCA2 genes in a 3,552 Japanese whole-genome sequence dataset (3.5KJPNv2)

MUL1 gene polymorphisms and Parkinson’s disease risk

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