Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ankara University, Ankara, Turkey.
J Clin Lipidol. 2019 Jul-Aug;13(4):554-562. doi: 10.1016/j.jacl.2019.05.013. Epub 2019 May 30.
Intestinal lipid malabsorption, resulting from an impaired formation or secretion of chylomicrons and associated with severe hypobetalipoproteinemia (HBL), may be due to biallelic mutations in APOB (homozygous FHBL type-1), MTTP (abetalipoproteinemia), or SAR1B (chylomicron retention disease).
We investigated four children, each born from consanguineous parents, presenting with steatorrhea, malnutrition, accumulation of lipids in enterocytes, and severe hypocholesterolemia with an apparent recessive transmission.
We sequenced a panel of genes whose variants may be associated with HBL.
Case 1, a 9-month-old male, was found to be homozygous for a SAR1B variant (c.49 C>T), predicted to encode a truncated Sar1b protein devoid of function (p.Gln17*). Case 2, a 4-year-old male, was found to be homozygous for a SAR1B missense variant [c.409 G>C, p.(Asp137His)], which affects a highly conserved residue close to the Sar1b guanosine recognition site. Case 3, a 6-year-old male, was found to be homozygous for an ∼6 kb deletion of the SAR1B gene, which eliminates exon 2; this deletion causes the loss of the ATG translation initiation codon in the SAR1B mRNA. The same homozygous mutation was found in an 11-month-old child (case 4) who was related to case 3.
We report 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene.
由于乳糜微粒的形成或分泌受损，导致肠道脂质吸收不良，并伴有严重的低β脂蛋白血症（HBL），这可能是由于 APOB（纯合 FHBL 型-1）、MTTP（无β脂蛋白血症）或 SAR1B（乳糜微粒滞留病）的双等位基因突变所致。
我们研究了 4 名来自近亲的患儿，他们均表现出脂肪泻、营养不良、肠细胞内脂质堆积和严重的低胆固醇血症，且表现出明显的隐性遗传方式。
我们对一组可能与 HBL 相关的基因突变进行了测序。
病例 1，一名 9 月龄男性，被发现为 SAR1B 变异（c.49C>T）的纯合子，该变异预测编码一个无功能的截断 Sar1b 蛋白（p.Gln17*）。病例 2，一名 4 岁男性，被发现为 SAR1B 错义变异（c.409G>C，p.（Asp137His））的纯合子，该变异影响靠近 Sar1b 鸟苷识别位点的高度保守残基。病例 3，一名 6 岁男性，被发现为 SAR1B 基因约 6kb 的缺失纯合子，该缺失消除了外显子 2；该缺失导致 SAR1B mRNA 中失去 ATG 翻译起始密码子。在与病例 3 相关的 11 月龄儿童（病例 4）中也发现了相同的纯合突变。
我们报道了 4 名儿童因 SAR1B 基因中的 3 个新变异而患有乳糜微粒滞留病，导致肠道脂质吸收不良。
