de Serpa Brandão Rafael Melo Santos, Britto Fábio Barros, do Monte Neto José Tiburcio, Lima Marcelo Cunha, do Monte Semiramis Jamil Hadad, de Sousa Lima Antonio Vanildo, Pereira Ester Miranda, da Silva Higo José Neri, Oliveira Deylane Menezes Teles E, Coelho Antonio Gilberto Borges, da Silva Adalberto Socorro
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.
Department of Biology, Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella - SG 01. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.
Mol Genet Metab Rep. 2022 Jan 3;30:100840. doi: 10.1016/j.ymgmr.2021.100840. eCollection 2022 Mar.
Lecithin-cholesterol acyltransferase (LCAT), an enzyme that participates in lipoprotein metabolism, plays an important role in cholesterol homeostasis. Mutations in the 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.
卵磷脂胆固醇酰基转移酶（LCAT）是一种参与脂蛋白代谢的酶，在胆固醇稳态中起重要作用。该基因的突变可导致两种罕见的遗传疾病：家族性LCAT缺乏症（FLD），其特征为角膜混浊、正细胞性贫血、血脂异常和蛋白尿，进而发展为慢性肾衰竭；以及鱼眼病（FED），其导致血脂异常和进行性角膜混浊。在此，我们报告了位于巴西东北部皮奥伊偏远地区的6例疑似FLD病例。对先证者进行了基因诊断。其中，对这些家庭中的新病例进行了进一步调查。此外，进行了分子分析以核实家庭内部的近亲程度以及他们之间是否存在遗传关系。所有6例先证者均被确诊为FLD，具有相同的突变（c.803G>A，p.R268H）。基因调查又确诊了7例新的FLD病例、52例杂合子和6例无突变个体。近亲结婚率表明，家族内部的婚姻并非导致该受限地区FLD病例数量众多的原因。对每个家庭的长辈（族长和女族长）进行了亲缘关系分析，结果显示他们彼此之间的遗传关系比对照组更为密切。实施贝叶斯分析以证实族长和女族长之间存在联系的假设，结果表明他们彼此之间的遗传关系比随机预期的更为密切，从而表明这些家庭可能存在奠基者效应。
