Autosomal Recessive Hypercholesterolemia: A Rare Cause of Familial Hypercholesterolemia

Kosmas, Constantine E.

doi:10.26717/bjstr.2017.01.000466

Cited by 1 publication

(1 citation statement)

References 9 publications

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“…Therefore, LDRAP1 :c.604delT was classified as PV for this present study, with a potential caveat that the phenotypic presentation is only expected when variants are presented in homozygous forms, given its autosomal recessive mode of inheritance. However, several studies have reported that subjects affected with heterozygous LDLRAP1 variants were associated with mild hypercholesterolaemia [ 10 , 100 ], but the effect of those heterozygous LDLRAP1 variants can only be definitively confirmed through extensive family screening and functional studies [ 10 , 100 ]. These LDLRAP1 variants, however, have not been previously reported in the Malaysian population and thus are likely to be novel variants in the Malaysian population.…”

Section: Discussionmentioning

confidence: 99%

Genetic Spectrum of Familial Hypercholesterolaemia in the Malaysian Community: Identification of Pathogenic Gene Variants Using Targeted Next-Generation Sequencing

Razman

Chua

Kasim

et al. 2022

IJMS

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Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.

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