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

• Abetalipoproteinemia (ABL) is a rare monogenic familial hypobetalipoproteinemia caused by bi-allelic variants in MTTP gene. • We identified four French-Canadian patients homozygous for the same MTTP variant. • The ABL carrier frequency in Saguenay-Lac-Saint-Jean is estimated at 1:203. • This represents the 2^nd highest worldwide carrier estimates for ABL. • Screening for ABL should be considered in this population. 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. [ABSTRACT FROM AUTHOR]