Publication Date
4-16-2024
Journal
BMC Medical Genomics
DOI
10.1186/s12920-024-01852-4
PMID
38622594
PMCID
PMC11020671
PubMedCentral® Posted Date
4-16-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Retrospective Studies, Siblings, Homozygote, Genome, Human, Polymorphism, Single Nucleotide, Biological Variation, Population, Genotype, Exome sequencing, Runs-of-homozygosity, Multilocus pathogenic variation, Neurodevelopmental disorders
Abstract
BACKGROUND: Multilocus pathogenic variants (MPVs) are genetic changes that affect multiple gene loci or regions of the genome, collectively leading to multiple molecular diagnoses. MPVs may also contribute to intrafamilial phenotypic variability between affected individuals within a nuclear family. In this study, we aim to gain further insights into the influence of MPVs on a disease manifestation in individual research subjects and explore the complexities of the human genome within a familial context.
METHODS: We conducted a systematic reanalysis of exome sequencing data and runs of homozygosity (ROH) regions of 47 sibling pairs previously diagnosed with various neurodevelopmental disorders (NDD).
RESULTS: We found siblings with MPVs driven by long ROH regions in 8.5% of families (4/47). The patients with MPVs exhibited significantly higher F
CONCLUSION: This study sheds light on the significance of considering MPVs in families with affected sibling pairs and the role of ROH as an adjuvant tool in explaining clinical variability within families. Identifying individuals carrying MPVs may have implications for disease management, identification of possible disease risks to different family members, genetic counseling and exploring personalized treatment approaches.
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons
Comments
This article has been corrected. See BMC Med Genomics. 2024 Aug 7;17:201.
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