Background: The genetic substrate of severe hypertriglyceridemia (sHTG) in Latin America is insufficiently understood.
Objective: To identify genetic variants in genes related to triglyceride (TG) metabolism among adults with sHTG from Colombia.
Methods: In individuals with plasma TG≥880 mg/dL at least once in their lifetime, we amplified and sequenced all exons and intron/exon boundaries of the genes LPL, APOC2, APOA5, GPIHBP1 and LMF1. For each variant we ascertained its location, zygosity, allelic frequency and pathogenicity classification according to American College of Medical Genetics (ACMG) criteria.
Results: The study included 166 participants (62 % male, mean age 50), peak TG levels ranged between 894 and 11,000 mg/dL. We identified 92 variants: 19 in LPL, 7 in APOC2, 11 in GPIHBP1, 38 in LMF1, and 17 in APOA5. Eighteen of these variants had not been reported. We identified a new pathogenic variant in LMF1 (c.41C>A; p.Ser14*), a new likely pathogenic variant in LMF1 (c.1527 C > T; p.Pro509=, also expressed as c.1447C>T; p.Gln483*), and a known pathogenic variant in LMF1 (c.779G>A; p.Trp260*). Four participants were heterozygous for variant c.953A>G; p.Asn318Ser in LPL, a known risk factor for hypertriglyceridemia. Participants with variants of unknown significance (VUS) in LMF1 had significantly higher peak TG than those with VUS in other genes. Peak TG were 4317 mg/dL in participants with a history of pancreatitis, and 1769 mg/dL in those without it (p = 0.001).
Conclusion: Our study identified variants associated with sHTG among Latinos, and showed that genetic variation in LMF1 may be frequently associated with sHTG in this population.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jacl.2024.08.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A crucial active site network of titratable residues guides catalysis and NAD binding in human succinic semialdehyde dehydrogenase.
Protein Sci
January 2025
Department of Neuroscience, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
Human succinic semialdehyde dehydrogenase is a mitochondrial enzyme fundamental in the neurotransmitter γ-aminobutyric acid catabolism. It catalyzes the NAD-dependent oxidative degradation of its derivative, succinic semialdehyde, to succinic acid. Mutations in its gene lead to an inherited neurometabolic rare disease, succinic semialdehyde dehydrogenase deficiency, characterized by mental and developmental delay.
View Article and Find Full Text PDFFamily Genetic Risk Communication and Reverse Cascade Testing in the BabySeq Project.
Genet Med
December 2024
Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Purpose: Genomic sequencing of newborns (NBSeq) can initiate disease surveillance and therapy for children, and may identify at-risk relatives through reverse cascade testing. We explored genetic risk communication and reverse cascade testing among families of newborns who underwent exome sequencing and had a risk for autosomal dominant disease identified.
Methods: We conducted semi-structured interviews with parents of newborns enrolled in the BabySeq Project who had a pathogenic or likely-pathogenic (P/LP) variant associated with an autosomal dominant (AD) childhood- and/or adult-onset disease returned.
Quantitative natural history modeling of HPDL-related disease based on cross-sectional data reveals genotype-phenotype correlations.
Genet Med
December 2024
Movement Disorders Program, Department of Neurology and F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:
Objectives: Biallelic HPDL variants have been identified as the cause of a progressive childhood-onset movement disorder, with a broad clinical spectrum from severe neurodevelopmental disorder to juvenile-onset pure hereditary spastic paraplegia type 83. This study aims at delineating the geno- and phenotypic spectra of patients with HPDL-related disease, quantitatively modelling the natural history, and uncovering genotype-phenotype associations.
Methods: A cross-sectional analysis of 90 published and one novel case was performed, employing a Human Phenotype Ontology-based approach.
From spastic paraplegia to infantile neurodegenerative disorder: Expanding the phenotypic spectrum associated with biallelic SPAST variants.
Eur J Neurol
January 2025
Service de Génétique Médicale, CHU Bordeaux, Bordeaux, France.
Purpose: Heterozygous pathogenic variants in SPAST are known to cause Hereditary Spastic Paraplegia 4 (SPG4), the most common form of HSP, characterized by progressive bilateral lower limbs spasticity with frequent sphincter disorders. However, there are very few descriptions in the literature of patients carrying biallelic variants in SPAST.
Methods: Targeted Sanger sequencing, panel sequencing and exome sequencing were used to identify the genetic causes in 9 patients from 6 unrelated families with symptoms of HSP or infantile neurodegenerative disorder.
Variant Spectrum of Renal Ciliopathies in Turkish Cohort and Genotype-Phenotype Association Specifically in Autosomal Dominant Polycystic Kidney Disease.
Clin Genet
December 2024
Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey.
Renal ciliopathies are a genetically and phenotypically heterogeneous group of diseases characterized by cystic and dysplastic kidneys. The aim of this study was to investigate the correlation between genetic changes that cause renal ciliopathies and phenotypic outcomes. The study group consisted of 137 patients diagnosed with renal ciliopathy disease.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!