Background

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).

Objective

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.

Methods

We sequenced a panel of genes whose variants may be associated with HBL.

Results

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.

Conclusions

We report 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene.

中文翻译：

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四个乳糜微粒保留病患儿SAR1B基因的新突变。

背景

乳糜微粒的形成或分泌受损导致的肠道脂质吸收不良，并伴有严重的低脂蛋白血症（HBL），可能是由于APOB（纯合子FHBL Type-1），MTTP（abetalipoproteinemia）或SAR1B（乳糜微粒retention留病）的双等位基因突变引起的。

客观的

我们调查了四个孩子，每个孩子都来自近亲的父母，他们表现出脂肪泻，营养不良，肠细胞中脂质蓄积和严重的低胆固醇血症，并伴有明显的隐性传播。

方法

我们对一组可能与HBL相关的基因进行了测序。

结果

病例1，一个9个月大的男性，被发现与SAR1B变体纯合（c.49 C> T），预计可编码无功能的截短Sar1b蛋白（p.Gln17 *）。案例2，一个4岁的男性，被发现是SAR1B错义变体的纯合子[c.409 G> C，p。（Asp137His）]，它影响了Sar1b鸟苷识别位点附近的高度保守的残基。案例3，一个6岁的男性，被发现是SAR1B基因约6 kb缺失的纯合子，该基因消除了外显子2。该缺失导致SAR1B mRNA中ATG翻译起始密码子的丢失。在与病例3相关的11个月大的孩子（病例4）中发现了相同的纯合突变。

结论

我们报告4小儿肠道脂质吸收不良被发现由于SAR1B基因中的3个新变体而有乳糜微粒保留病。