What does this research mean for the field?

A residual 20% LCAT alpha-activity in compound heterozygous fish-eye disease is sufficient to normalize the CE/TC ratio but does not prevent the development of corneal opacity. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

Characterize a compound heterozygous patient presenting with fish-eye disease and determine the functional impact of a novel LCAT gene variant on enzyme activity and lipid profiles.

October 2, 2024Journal of clinical lipidologyOpen Access

Novel pathogenic variant in the LCAT gene in a compound heterozygous patient with fish-eye disease and a mild phenotype

Q: What is the clinical evidence from this study?

Study design: Case Report. Population: Fish-eye disease (n=1). Intervention: Compound heterozygous LCAT gene variants (p.Pro34Leu/p.Asn154Asp) vs. Normolipidemic controls and typical FED-causing variant. Primary outcome: LCAT α-activity.

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Key result

Novel compound heterozygous LCAT variants retain ~20% alpha-activity and normalize CE/TC, but fail to prevent corneal opacity.

Key Points

Characterize a compound heterozygous patient presenting with fish-eye disease and determine the functional impact of a novel LCAT gene variant on enzyme activity and lipid profiles.
Assayed plasma LCAT activity and sequenced the LCAT gene using the proband's blood samples.
Performed an in vitro expression assay to compare the activity of the newly identified LCAT variant against wild-type and known disease-causing variants.
The proband retained approximately 20% LCAT α-activity relative to normolipidemic controls and maintained a normal cholesteryl ester to total cholesterol ratio, contrasting with typical variants exhibiting only 3% activity.
Identified compound heterozygous mutations consisting of the known p.Pro34Leu variant and a novel p.Asn154Asp substitution in the LCAT gene.
In vitro expression confirmed that p.Asn154Asp significantly reduced LCAT α-activity compared to wild-type, though function remained relatively higher than in typical fish-eye disease variants.

Study Design

Type

Case Report (n=1)

Structured PICO

Population

A case report of a patient with compound heterozygous fish-eye disease presenting with a cholesteryl ester/total cholesterol ratio within the reference range.

Exposure

LCAT activity assays, genetic analyses, and in vitro expression assays

Comparator

Normolipidemic controls and a patient with a typical FED-causing variant (p.Thr147Ile)

Outcome

LCAT α-activity and identification of LCAT gene variantssurrogate

Main Result

Absolute Event Rate: 20% vs 3%

Discussion

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Implication

A residual 20% LCAT α-activity is sufficient to normalize the CE/TC ratio but not to prevent corneal opacity in fish-eye disease.

Cite This Study

Miyata et al. (2024) conducted a case report in Fish-eye disease (n=1). Compound heterozygous LCAT gene variants (p.Pro34Leu/p.Asn154Asp) vs. Normolipidemic controls and typical FED-causing variant was evaluated on LCAT α-activity. A proband with novel compound heterozygous LCAT variants (p.Pro34Leu/p.Asn154Asp) retained 20% LCAT α-activity, which normalized the CE/TC ratio but did not prevent corneal opacity.

synapsesocial.com/papers/6a0ba91c4f6759c6fca254ab https://doi.org/10.1016/j.jacl.2024.09.013

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Novel pathogenic variant in the LCAT gene in a compound heterozygous patient with fish-eye disease and a mild phenotype

Key Points

Study Design

Structured PICO

Main Result

Discussion

Implication

Cite This Study

Novel pathogenic variant in the LCAT gene in a compound heterozygous patient with fish-eye disease and a mild phenotype

Key Points

Study Design

Structured PICO

Main Result

Discussion

Implication

Cite This Study

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