{"title":"在一个法裔加拿大人群体中,无胎盘脂蛋白血症的携带者频率很高,而且有证据表明这是一种创始变异体","authors":"","doi":"10.1016/j.jacl.2024.04.132","DOIUrl":null,"url":null,"abstract":"<div><p><span>Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (</span><em>MTTP</em>) 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 <em>MTTP</em> 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.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"18 4","pages":"Pages e625-e630"},"PeriodicalIF":3.6000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High carrier frequency for abetalipoproteinemia and evidence of a founder variant in a French-Canadian population\",\"authors\":\"\",\"doi\":\"10.1016/j.jacl.2024.04.132\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (</span><em>MTTP</em>) 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 <em>MTTP</em> 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.</p></div>\",\"PeriodicalId\":15392,\"journal\":{\"name\":\"Journal of clinical lipidology\",\"volume\":\"18 4\",\"pages\":\"Pages e625-e630\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of clinical lipidology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1933287424001806\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of clinical lipidology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1933287424001806","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
无脂蛋白血症(ABL)是一种罕见的隐性遗传病,由微粒体甘油三酯转移蛋白()基因中的双等位基因致病变异引起。这种疾病的特征是含脂蛋白 B 的脂蛋白分泌不足。ABL 患者由于脂肪吸收不良和缺乏脂溶性维生素,会出现神经、血液和胃肠道症状。在本报告中,我们共发现了四例 ABL 病例,其中包括三例新病例,均来自加拿大魁北克省萨格奈-拉克-圣让地区的同一法裔加拿大人始祖群体。这些人都是基因中同一致病变体(c.419dup, p.Asn140Lysfs*2)的同源基因携带者。我们发现,在这一人群中,这种变异比预期的更为常见,估计携带者频率为 1:203。早期诊断对于启动已知的治疗以预防 ABL 相关并发症至关重要。在这一法裔加拿大人创始人群中,应考虑进行人群携带者筛查或新生儿ABL筛查。
High carrier frequency for abetalipoproteinemia and evidence of a founder variant in a French-Canadian 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.
期刊介绍:
Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. While preference is given to material of immediate practical concern, the science that underpins lipidology is forwarded by expert contributors so that evidence-based approaches to reducing cardiovascular and coronary heart disease can be made immediately available to our readers. Sections of the Journal will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.