Towards efficiency in rare disease research: what is distinctive and important?

Jia, Jinmeng; Shi, Tieliu

doi:10.1007/s11427-017-9099-3

Cited by 27 publications

(26 citation statements)

References 38 publications

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“…However, this was reported in a single patient without an epilepsy phenotype. Therefore, reports of additional patients are needed to define the relationship between genotype and phenotype in DNM1 mutation-related epileptic encephalopathy (Jia and Shi, 2017). EEG is an important tool for assessment of the diagnosis and prognosis of epileptic encephalopathy in patients carrying DNM1 mutations.…”

Section: Discussionmentioning

confidence: 99%

Clinical Assessments and EEG Analyses of Encephalopathies Associated With Dynamin-1 Mutation

Fang

et al. 2019

Front. Pharmacol.

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Epileptic encephalopathy, caused by mutations in the dynamin-1 (DNM1; NM_004408) gene, is a newly identified neurologic disorder in children. Thus far, the full clinical and electroencephalographic features of children with DNM1 mutation-related epileptic encephalopathy have not been established. The aim of this study is to characterize the phenotypic, genetic, and electroencephalographic features of children with DNM1 mutation-related epileptic encephalopathy. Here, we investigated a patient with a novel pathogenic DNM1 variant, who received treatment in Beijing Children's Hospital and had detailed clinical, EEG, and genetic information. Conversely, we performed an extensive literature search in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, China National Knowledge Infrastructure, and Wanfang Database using the term "DNM1" and were able to find 32 cases reported in nine articles (in English) from January 2013 to December 2018. The clinical features of 33 cases with pathogenic DNM1 variants were analyzed and the results showed that patients carrying pathogenic variants in the GTPase or middle domains present with epileptic encephalopathy and severe neurodevelopmental symptoms. Patients carrying pathogenic variants in both domains exhibited comparable phenotypes.

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Section: Discussionmentioning

confidence: 99%

Clinical Assessments and EEG Analyses of Encephalopathies Associated With Dynamin-1 Mutation

Fang

et al. 2019

Front. Pharmacol.

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“…Next generation sequencing has been widely used to decipher the underlying variants for rare disease (Jia and Shi, 2017; Qi et al, 2017). Here, we report that WGS of germline DNA in two brothers with HB and their unaffected parents revealed two independent mutations in APC and WAS .…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis

et al. 2018

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Hepatoblastoma (HB), a leading primary hepatic malignancy in children, originates from primitive hepatic stem cells. This study aimed to uncover the genetic variants that are responsible for HB oncogenesis. One family, which includes the healthy parents, and two brothers affected by HB, was recruited. Whole-genome sequencing (WGS) of germline DNA from all the family members identified two maternal variants, located within APC gene and X-linked WAS gene, which were harbored by the two brothers. The mutation of APC (rs137854573, c.C1606T, p.R536X) could result in HB carcinogenesis by activating Wnt signaling. The WAS variant (c.G3T, p.M1-P5del) could promote HB cell proliferation and inhibit T-cell-based immunity by activating PLK1 signaling and inactivating TCR signaling. Further analysis reflected that WAS deficiency might affect the antitumor activity of natural killer and dendritic cells. In summary, the obtained results imply that an APC mutant together with an X-linked WAS mutant, could lead to HB tumorigenesis by activating Wnt and PLK1 signaling, inhibiting TCR signaling, and reducing the antitumor activity of natural killer and dendritic cells.

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“…Currently, there is no unified, widely accepted definition for rare diseases, and rare diseases vary in prevalence throughout different populations ( 6 ). A need for collaboration across different countries has long been proposed to facilitate better definition, data sharing and diagnosis of rare diseases ( 7 ).…”

Section: Disease Definitionmentioning

confidence: 99%

eRAM: encyclopedia of rare disease annotations for precision medicine

Jia

Ming

et al. 2017

Nucleic Acids Research

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Rare diseases affect over a hundred million people worldwide, most of these patients are not accurately diagnosed and effectively treated. The limited knowledge of rare diseases forms the biggest obstacle for improving their treatment. Detailed clinical phenotyping is considered as a keystone of deciphering genes and realizing the precision medicine for rare diseases. Here, we preset a standardized system for various types of rare diseases, called encyclopedia of Rare disease Annotations for Precision Medicine (eRAM). eRAM was built by text-mining nearly 10 million scientific publications and electronic medical records, and integrating various data in existing recognized databases (such as Unified Medical Language System (UMLS), Human Phenotype Ontology, Orphanet, OMIM, GWAS). eRAM systematically incorporates currently available data on clinical manifestations and molecular mechanisms of rare diseases and uncovers many novel associations among diseases. eRAM provides enriched annotations for 15 942 rare diseases, yielding 6147 human disease related phenotype terms, 31 661 mammalians phenotype terms, 10,202 symptoms from UMLS, 18 815 genes and 92 580 genotypes. eRAM can not only provide information about rare disease mechanism but also facilitate clinicians to make accurate diagnostic and therapeutic decisions towards rare diseases. eRAM can be freely accessed at http://www.unimd.org/eram/.

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Towards efficiency in rare disease research: what is distinctive and important?

Cited by 27 publications

References 38 publications

Clinical Assessments and EEG Analyses of Encephalopathies Associated With Dynamin-1 Mutation

Clinical Assessments and EEG Analyses of Encephalopathies Associated With Dynamin-1 Mutation

Whole-Genome Sequencing Identifies a Novel Variation of WAS Gene Coordinating With Heterozygous Germline Mutation of APC to Enhance Hepatoblastoma Oncogenesis

eRAM: encyclopedia of rare disease annotations for precision medicine

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