Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.
Circ Genom Precis Med
; 17(2): e004457, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38506081
ABSTRACT
BACKGROUND:
Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P/LP) variants in the LDLR gene in female individuals receiving reproductive carrier screening.METHODS:
This retrospective observational study included samples from female patients (aged 18-55 years) receiving a 274-gene carrier screening panel from January 2020 to September 2022. LDLR exons and their 10 base pair flanking regions were sequenced. Carrier frequency for P/LP variants was calculated for the entire population and by race/ethnicity. The most common variants and their likely functional effects were evaluated.RESULTS:
A total of 91â 637 tests were performed on women with race/ethnicity reported as Asian (8.8%), Black (6.1%), Hispanic (8.5%), White (29.0%), multiple or other (15.0%), and missing (33.0%). Median age was 32.8 years with 83â 728 (91%) <40 years. P/LP LDLR variants were identified in 283 samples (1 in 324). No patients were identified with >1 P/LP variant. LDLR carrier frequency was higher in Asian (1 in 191 [95% CI, 1 in 142-258]) compared with White (1 in 417 [95% CI, 1 in 326-533]; P<0.001) or Black groups (1 in 508 [95% CI, 1 in 284-910]; P=0.004). The most common variants differed between populations. Of all variants, at least 25.0% were predicted as null variants.CONCLUSIONS:
P/LP variants in LDLR are common. Expanding the use of reproductive carrier screening to include genes associated with FH presents another opportunity to identify people predisposed to cardiovascular disease.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
/
Hiperlipoproteinemia Tipo II
Limite:
Adolescent
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Adult
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Female
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Humans
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Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Circ Genom Precis Med
Ano de publicação:
2024
Tipo de documento:
Article