Clinical and functional evidence supporting pathogenicity of a novel APOA5 variant in familial chylomicronemia syndrome.

Authors

Johnayro Gutiérrez, Pablo Castaño, Claudia Monsalve, Nestor López, Fernando Rivera Toquica, Edwin Mora, Jessica Cristina Armijos, Juliana Lores, Henry Mauricio Arenas, Germán Camilo Giraldo, Diana Sánchez, Natalia Agudelo, Gregorio Fariña, Gabriela Berg, Juan Patricio Nogueira

Published in

Archives of endocrinology and metabolism. Volume 70. Issue 5. Pages e260101. Sep 10, 2026. Epub Sep 10, 2026.

Abstract

This study aimed to evaluate the clinical and functional impact of a novel apolipoprotein A5 (ApoA5) variant by assessing lipoprotein lipase (LPL) activity.
Demographic and clinical data, including blood lipid levels and body mass index, were retrospectively collected from an endocrinology clinic registry. Ten individuals with familial chylomicronemia syndrome (FCS) carrying a novel APOA5 variant were included. Whole-exome sequencing was performed using the latest generation DNB-SEQ400 platform. LPL activity was measured in post-heparin plasma using a radiometric assay. Statistical analysis: Categorical variables were summarized as frequencies and percentages, and continuous variables as mean ± standard deviation or median (range), as appropriate. Group comparisons were performed using the Mann-Whitney U test or chi-square test. Analyses were conducted using the Statistical Package for the Social Sciences software (v. 25.0). A p-value < 0.05 was considered statistically significant.
We report ten cases of FCS with a homozygous missense variant of uncertain significance in APOA5: c.694T>C; p.(Ser232Pro), located in exon 3. In six patients assessed for LPL activity, levels remained consistently below 20% compared to normotriglyceridemic controls. The addition of exogenous serum containing APOA5 restored LPL activity to above 20% in all cases, indicating functional rescue.
Measurement of LPL activity demonstrated the functional impact of the APOA5 c.694T>C; p.(Ser232Pro) variant. These findings support reclassification of the variant as likely pathogenic and enable differentiation from multifactorial chylomicronemia syndrome.

PMID:
42721061
Bibliographic data and abstract were imported from PubMed on 11 Sep 2026.

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