Ontology highlight
ABSTRACT: Purpose
We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology.Methods
We enrolled 52 FH probands with a pathogenic variant (FHg+) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FHg-). After direct contact by the study team, family members (FMs) of FHg+ probands could opt-in for genetic testing and FMs of FHg- probands were asked to provide a lipid profile. New cases were defined as presence of a pathogenic variant in FHg+ families and as low-density lipoprotein cholesterol ≥155 mg/dL in FHg- families.Results
Of 71 FHg+ probands seen by a genetic counselor, 52 consented and identified 253 FMs (111 consented and were tested, yielding 48 new cases). Of 101 FHg- probands who received counseling, 73 consented and identified 295 FMs (63 consented and were tested, yielding 17 new cases). New case detection per index case was significantly greater in FHg+ than in FHg- families (0.92 vs 0.23), a result of higher cascade testing uptake (43.9 vs 21.4%) and yield (43.2 vs 27.0%) in the former.Conclusion
New case detection rate was significantly higher in FH families with a monogenic etiology than in those without such an etiology owing to greater uptake and yield of cascade testing.
SUBMITTER: Miller AA
PROVIDER: S-EPMC9944844 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Miller Alexandra A AA Bangash Hana H Smith Carin Y CY Wood-Wentz Christina M CM Bailey Kent R KR Kullo Iftikhar J IJ
Genetics in medicine : official journal of the American College of Medical Genetics 20220929 12
<h4>Purpose</h4>We compared new cases detected per index case in familial hypercholesterolemia (FH) families with or without an identifiable monogenic etiology.<h4>Methods</h4>We enrolled 52 FH probands with a pathogenic variant (FH<sup>g+</sup>) in LDLR, APOB, or PCSK9 and 73 probands without such a variant (FH<sup>g-</sup>). After direct contact by the study team, family members (FMs) of FH<sup>g+</sup> probands could opt-in for genetic testing and FMs of FH<sup>g-</sup> probands were asked to ...[more]