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

Autor: Guay SP; 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)., Paquette M; Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada (Drs Guay, Paquette, Gosse, Poulin, and Baass)., Girard L; Department of Biochemistry and Functional Genomics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada (Drs Girard, Desgagné, and Bouchard)., Desgagné V; 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)., Gosse G; Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada (Drs Guay, Paquette, Gosse, Poulin, and Baass)., Poulin V; Genetic Dyslipidemias Clinic of the Montreal Clinical Research Institute, Montréal, Québec, Canada (Drs Guay, Paquette, Gosse, Poulin, and Baass)., Bouchard L; 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)., Baass A; 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: aass@ircm.qc.ca.
Jazyk: angličtina
Zdroj: Journal of clinical lipidology [J Clin Lipidol] 2024 Jul-Aug; Vol. 18 (4), pp. e625-e630. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1016/j.jacl.2024.04.132
Abstrakt: 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.
Competing Interests: Declaration of competing interest AB received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals, Inc., ISIS Pharmaceuticals, The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. SPG, MP, LG, GG, VD, VP, and LB have no conflict of interest to declare.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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