Dataset Information

The Genetic Control of the Rheumatic Heart: Closing the Genotype-Phenotype Gap.

ABSTRACT: Rheumatic heart disease (RHD) is a heritable inflammatory condition characterized by carditis, arthritis, and systemic disease. Although remaining neglected, the last 3 years has seen some promising advances in RHD research. Whilst it is clear that RHD can be triggered by recurrent group A streptococcal infections, the mechanisms driving clinical progression are still poorly understood. This review summarizes our current understanding of the genetics implicated in this process and the genetic determinants that predispose some people to RHD. The evidence demonstrating the importance of individual cell types and cellular states in delineating causal genetic variants is discussed, highlighting phenotype/genotype correlations where possible. Genetic fine mapping and functional studies in extreme phenotypes, together with large-scale omics studies including genomics, transcriptomics, epigenomics, and metabolomics, are expected to provide new information not only on RHD but also on the mechanisms of other autoimmune diseases and facilitate future clinical translation.

SUBMITTER: Abdallah AM

PROVIDER: S-EPMC8024521 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundMutations in LRRK2, the gene that encodes leucine-rich repeat kinase 2, are a cause of Parkinson's disease (PD). The International LRRK2 Consortium was established to answer three key clinical questions: can LRRK2-associated PD be distinguished from idiopathic PD; which mutations in LRRK2 are pathogenic; and what is the age-specific cumulative risk of PD for individuals who inherit or are at risk of inheriting a deleterious mutation in LRRK2?MethodsResearchers from 21 centres across the world collaborated on this study. The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. The LRRK2 phenotype was defined on the basis of 59 motor and non-motor symptoms in 356 patients with LRRK2-associated PD and compared with the symptoms of 543 patients with pathologically proven idiopathic PD.FindingsSix mutations met the consortium's criteria for being proven pathogenic. The frequency of the common LRRK2 Gly2019Ser mutation was 1% of patients with sporadic PD and 4% of patients with hereditary PD; the frequency was highest in the middle east and higher in southern Europe than in northern Europe. The risk of PD for a person who inherits the LRRK2 Gly2019Ser mutation was 28% at age 59 years, 51% at 69 years, and 74% at 79 years. The motor symptoms (eg, disease severity, rate of progression, occurrence of falls, and dyskinesia) and non-motor symptoms (eg, cognition and olfaction) of LRRK2-associated PD were more benign than those of idiopathic PD.InterpretationMutations in LRRK2 are a clinically relevant cause of PD that merit testing in patients with hereditary PD and in subgroups of patients with PD. However, this knowledge should be applied with caution in the diagnosis and counselling of patients.FundingUK Medical Research Council; UK Parkinson's Disease Society; UK Brain Research Trust; Internationaal Parkinson Fonds; Volkswagen Foundation; National Institutes of Health: National Institute of Neurological Disorders and Stroke and National Institute of Aging; Udall Parkinson's Disease Centre of Excellence; Pacific Alzheimer Research Foundation Centre; Italian Telethon Foundation; Fondazione Grigioni per il Morbo di Parkinson; Michael J Fox Foundation for Parkinson's Research; Safra Global Genetics Consortium; US Department of Veterans Affairs; French Agence Nationale de la Recherche.

Dataset Information

The Genetic Control of the Rheumatic Heart: Closing the Genotype-Phenotype Gap.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets