Familial lecithin-cholesterol acyltransferase deficiency: If so rare, why so frequent in the state of Piauí, northeastern Brazil?

Rafael Melo Santos de Serpa Brandão; Fábio Barros Britto; José Tiburcio do Monte Neto; Marcelo Cunha Lima; Semiramis Jamil Hadad do Monte; Antonio Vanildo de Sousa Lima; Ester Miranda Pereira; Higo José Neri da Silva; Deylane Menezes Teles E Oliveira; Antonio Gilberto Borges Coelho; Adalberto Socorro da Silva

doi:10.1016/j.ymgmr.2021.100840

Familial lecithin-cholesterol acyltransferase deficiency: If so rare, why so frequent in the state of Piauí, northeastern Brazil?

Mol Genet Metab Rep. 2022 Jan 3:30:100840. doi: 10.1016/j.ymgmr.2021.100840. eCollection 2022 Mar.

Affiliations

¹ Laboratory of Immunogenetics and Molecular Biology, Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella - SG 16. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.
² Department of Biology, Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella - SG 01. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.
³ Department of General Practice - Nephrology, Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.
⁴ Universitary Hospital (HU-UFPI/EBSERH), Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.
⁵ Master's Program in Science and Health, Federal University of Piauí, Teresina, Brazil, Centro de Ciências da Saúde, Avenida Frei Serafim n° 2280. Bairro Centro, Teresina, Piauí 64001-020, Brazil.
⁶ Graduate Program in Biotechnology - RENORBIO, Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.

Abstract

Lecithin-cholesterol acyltransferase (LCAT), an enzyme that participates in lipoprotein metabolism, plays an important role in cholesterol homeostasis. Mutations in the LCAT gene can cause two rare genetic disorders: familial LCAT deficiency (FLD), which is characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure, and fish-eye disease (FED), which causes dyslipidemia and progressive corneal opacities. Herein, we report six suspected cases of FLD in the backlands of Piauí, located in northeast Brazil. A genetic diagnosis was performed in index cases. Among these, a further investigation was performed to identify new cases in the families. In addition, molecular analyses were performed to verify the levels of consanguinity within families and the existence of a genetic relationship between them. All six index cases were confirmed as FLD with an identical mutation (c.803G > A, p.R268H). The genetic investigation confirmed another 7 new cases of FLD, 52 heterozygous and 6 individuals without mutations. The rate of consanguinity revealed that marriages within the family did not contribute to the high number of FLD cases within the restricted region. The elders of each family (patriarchs and matriarchs) were subjected to a kinship analysis and were more genetically related to each other than the control group. Bayesian analysis was implemented to confirm the hypothesis of connectivity among patriarchs and matriarchs and indicated that they were genetically more related to each other than would be randomly expected, thus suggesting the occurrence of a possible founder effect in these families.

Keywords: Chronic kidney disease; FED, Fish-eye disease; FLD, familial lecithin-cholesterol acyltransferase deficiency; Genetic relatedness; HDL, high-density lipoprotein; High-density lipoproteins; LCAT, lecithin-cholesterol acyltransferase; Lecithin-cholesterol acyltransferase; Mutation; Rare disease.