Evidence map›Paper›PMID 39428697›Full record

ArticleAmerican journal of medical genetics. Part C, Seminars in medical genetics2024

Family Lore, a Variant of Uncertain Significance, and CADASIL.

Rhys Duarte, Liesbeth Vossaert, Sandra A Darilek, Chelsi Rose, Evan Schauer, Christian Parobek, Emily Bland, Keren Machol, Elizabeth Mizerik, Chaya N Murali

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PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of medical genetics. Part C, Seminars in medical genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Rhys DuarteDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.ORCID 0009-0000-9414-9540
Liesbeth VossaertDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Sandra A DarilekDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Chelsi RoseDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Evan SchauerDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Christian ParobekDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Emily BlandDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Keren MacholDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Elizabeth MizerikDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.
Chaya N MuraliDepartment of Molecular and Human Genetics, Baylor College of Medicine, Texas, USA.ORCID 0000-0002-9781-3387

Funding

MEDICAL GENETICS RESEARCH FELLOWSHIP PROGRAMT32GM007526 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Brendan Lee · 1985 to 2026
$11.4M
NIGMS NIH HHS T32 GM007526
6 · The paper itself

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.

Indexed as

CADASILAdultExome SequencingHumansInfantMaleMutationPedigreeReceptor, Notch3NOTCH3 protein, humanReceptor, Notch3CADASILcerebrovascular disordersfamily historygenetic diseasesinborn

Identifiers

PMID39428697
PMCPMC12619969

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.