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

J Clin Lipidol. 2024 Jul-Aug;18(4):e625-e630. doi: 10.1016/j.jacl.2024.04.132. Epub 2024 Apr 26.

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.

Keywords: Abetalipoproteinemia; Founder effect; French-Canadian; MTTP gene; Saguenay-Lac-Saint-Jean; Screening.

Publication types

  • Case Reports

MeSH terms

  • Abetalipoproteinemia* / genetics
  • Adult
  • Canada / epidemiology
  • Carrier Proteins* / genetics
  • Female
  • Founder Effect*
  • Gene Frequency
  • Heterozygote
  • Humans
  • Male
  • Quebec / epidemiology

Substances

  • microsomal triglyceride transfer protein
  • Carrier Proteins