Gonzaga-Jauregui Claudia, Mir Sabina, Penney Samantha, Jhangiani Shalini, Midgen Craig, Finegold Milton, Muzny Donna M, Wang Min, Bacino Carlos A, Gibbs Richard A, Lupski James R, Kellermayer Richard, Hanchard Neil A
*Department of Molecular and Human Genetics †Department of Pediatrics ‡Human Genome Sequencing Center §Section of Pediatric Pathology, Department of Pathology, Baylor College of Medicine, Houston, TX.
J Pediatr Gastroenterol Nutr. 2014 Jul;59(1):17-21. doi: 10.1097/MPG.0000000000000363.
Severe congenital hypertriglyceridemia (HTG) is a rare disorder caused by mutations in genes affecting lipoprotein lipase (LPL) activity. Here we report a 5-week-old Hispanic girl with severe HTG (12,031 mg/dL, normal limit 150 mg/dL) who presented with the unusual combination of lower gastrointestinal bleeding and milky plasma. Initial colonoscopy was consistent with colitis, which resolved with reduction of triglycerides. After negative sequencing of the LPL gene, whole-exome sequencing revealed novel compound heterozygous mutations in GPIHBP1. Our study broadens the phenotype of GPIHBP1-associated HTG, reinforces the effectiveness of whole-exome sequencing in Mendelian diagnoses, and implicates triglycerides in gastrointestinal mucosal injury.
严重先天性高甘油三酯血症（HTG）是一种由影响脂蛋白脂肪酶（LPL）活性的基因突变引起的罕见疾病。我们报告一名5周大的西班牙裔女孩，患有严重HTG（12,031mg/dL，正常上限为150mg/dL），出现下消化道出血和乳糜样血浆的不寻常组合。初始结肠镜检查结果与结肠炎相符，随着甘油三酯水平降低结肠炎得到缓解。在LPL基因测序结果为阴性后，全外显子组测序揭示了GPIHBP1基因存在新的复合杂合突变。我们的研究拓宽了与GPIHBP1相关的HTG的表型，强化了全外显子组测序在孟德尔疾病诊断中的有效性，并提示甘油三酯与胃肠道黏膜损伤有关。
