Language
English
Publication Date
11-1-2024
Journal
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
DOI
10.1002/ajmg.c.32117
PMID
39428697
PMCID
PMC12619969
PubMedCentral® Posted Date
11-17-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing. When the results reveal an unexpected, paternally inherited variant of uncertain significance (VUS) in NOTCH3, fresh questions arise. The infant's presenting symptoms and descriptive diagnoses, including hematemesis, epistaxis, and gastric ulcers, certainly do not fit the mold of CADASIL. However, closer inspection of his family history yields tantalizing clues: a father and paternal grandfather with seizures, and a paternal grandfather with unexplained mood disturbances in middle age. Combining details gleaned from the family history and medical literature, the clinical genetics and laboratory genetics team collaborated, reclassified the VUS as likely pathogenic, and offered a new unifying diagnosis to explain much of the family's lore.
Keywords
Humans, CADASIL, Male, Receptor, Notch3, Pedigree, Infant, Exome Sequencing, Mutation, Adult, CADASIL, cerebrovascular disorders, family history, genetic diseases, inborn
Published Open-Access
yes
Recommended Citation
Duarte, Rhys; Vossaert, Liesbeth; Darilek, Sandra A; et al., "Family Lore, a Variant of Uncertain Significance, and CADASIL" (2024). Faculty and Staff Publications. 5185.
https://digitalcommons.library.tmc.edu/baylor_docs/5185
Included in
Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons