The contribution of mosaicism to genetic diseases and de novo pathogenic variants.
Am J Med Genet A
; 191(10): 2482-2492, 2023 10.
Article
in En
| MEDLINE
| ID: mdl-37246601
ABSTRACT
The contribution of mosaicism to diagnosed genetic disease and presumed de novo variants (DNV) is under investigated. We determined the contribution of mosaic genetic disease (MGD) and diagnosed parental mosaicism (PM) in parents of offspring with reported DNV (in the same variant) in the (1) Undiagnosed Diseases Network (UDN) (N = 1946) and (2) in 12,472 individuals electronic health records (EHR) who underwent genetic testing at an academic medical center. In the UDN, we found 4.51% of diagnosed probands had MGD, and 2.86% of parents of those with DNV exhibited PM. In the EHR, we found 6.03% and 2.99% and (of diagnosed probands) had MGD detected on chromosomal microarray and exome/genome sequencing, respectively. We found 2.34% (of those with a presumed pathogenic DNV) had a parent with PM for the variant. We detected mosaicism (regardless of pathogenicity) in 4.49% of genetic tests performed. We found a broad phenotypic spectrum of MGD with previously unknown phenotypic phenomena. MGD is highly heterogeneous and provides a significant contribution to genetic diseases. Further work is required to improve the diagnosis of MGD and investigate how PM contributes to DNV risk.
Key words
Full text:
1
Collection:
01-internacional
Health context:
1_ASSA2030
Database:
MEDLINE
Main subject:
Genetic Variation
/
Mosaicism
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Am J Med Genet A
Year:
2023
Document type:
Article