High carrier frequency for abetalipoproteinemia and evidence of a founder variant in a French-Canadian population.

Véronique Desgagné, Simon-Pierre Guay, Martine Paquette, Alexis Baass, Luigi Bouchard, Lysanne Girard, Géraldine Gosse, Valérie Poulin

Journal: Journal of clinical lipidology 2024;18(4):e625-e630

PMID: 38908974

Full Text on Elsevier Science View on PubMed

Abstract

Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (MTTP) gene. This disease is characterized by a deficiency in the secretion of apolipoprotein B-containing lipoproteins. Patients with ABL present with neurological, hematological, and gastrointestinal symptoms due to fat malabsorption and a deficiency in liposoluble vitamins. In this report, we present a total of four ABL cases, including three new cases, all originating from the same French-Canadian founder population in Saguenay-Lac-Saint-Jean, Québec, Canada. These individuals are homozygous for the same pathogenic variant in the MTTP gene (c.419dup, p.Asn140Lysfs*2). We found that this variant is more common than anticipated in this population, with an estimated carrier frequency of 1:203. Early diagnosis is essential to initiate treatment known to prevent complications associated with ABL. Population carrier screening or newborn screening for ABL should be considered in this French-Canadian founder population.

Address: Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada (Drs Guay, Paquette, Gosse, Poulin, and Baass); Department of Medicine, Division of Endocrinology, Université de Montréal, Montréal, Québec, Canada (Dr Guay); Department of Pediatrics, Division of Medical Genetics, Université de Sherbrooke, Québec, Canada (Dr Guay).; Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada (Drs Guay, Paquette, Gosse, Poulin, and Baass).; Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada (Drs Girard, Desgagné, and Bouchard).; Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada (Drs Girard, Desgagné, and Bouchard); Clinical Department of Laboratory Medicine, Centre intégré universitaire de santé et de services sociaux (CIUSSS) du Saguenay-Lac-Saint-Jean - Hôpital de Chicoutimi, Saguenay, Québec, Canada (Drs Desgagné, Bouchard, and Baass).; Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada (Drs Guay, Paquette, Gosse, Poulin, and Baass); Department of Medicine, Divisions of Experimental Medicine and Medical Biochemistry, McGill University, Montréal, Québec, Canada (Dr Baass). Electronic address: [email protected].

DOI: 10.1016/j.jacl.2024.04.132

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MeSH Terms: Humans, Abetalipoproteinemia, Canada, Carrier Proteins, Founder Effect, Gene Frequency, Heterozygote, Quebec