Dataset Information

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.

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 91 637 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 83 728 (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.

SUBMITTER: Souter V

PROVIDER: S-EPMC11019987 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.

Souter Vivienne V Becraft Emily E Brummitt Samantha S Gall Bryan J BJ Prigmore Brittany B Wang Yang Y Benn Peter P

Circulation. Genomic and precision medicine 20240320 2

<h4>Background</h4>Familial hypercholesterolemia is a treatable genetic condition but remains underdiagnosed. We reviewed the frequency of pathogenic or likely pathogenic (P/LP) variants in the <i>LDLR</i> gene in female individuals receiving reproductive carrier screening.<h4>Methods</h4>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. <i>LDLR</i> exons and their 10 b ...[more]

PMID: 38506081

Similar Datasets

Project description:Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a "real-world" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

Dataset Information

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.

Background

Methods

Results

Conclusions

Publications

Reproductive Carrier Screening: Identifying Families at Risk for Familial Hypercholesterolemia in the United States.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets