Kantarci Sibel, Al-Gazali Lihadh, Hill R Sean, Donnai Dian, Black Graeme C M, Bieth Eric, Chassaing Nicolas, Lacombe Didier, Devriendt Koen, Teebi Ahmad, Loscertales Maria, Robson Caroline, Liu Tianming, MacLaughlin David T, Noonan Kristin M, Russell Meaghan K, Walsh Christopher A, Donahoe Patricia K, Pober Barbara R
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Simches Research Building, 185 Cambridge St., Boston, Massachusetts 02114 USA.
Nat Genet. 2007 Aug;39(8):957-9. doi: 10.1038/ng2063. Epub 2007 Jul 15.
Donnai-Barrow syndrome is associated with agenesis of the corpus callosum, congenital diaphragmatic hernia, facial dysmorphology, ocular anomalies, sensorineural hearing loss and developmental delay. By studying multiplex families, we mapped this disorder to chromosome 2q23.3-31.1 and identified LRP2 mutations in six families with Donnai-Barrow syndrome and one family with facio-oculo-acoustico-renal syndrome. LRP2 encodes megalin, a multiligand uptake receptor that regulates levels of diverse circulating compounds. This work implicates a pathway with potential pharmacological therapeutic targets.
唐纳-巴罗综合征与胼胝体发育不全、先天性膈疝、面部畸形、眼部异常、感音神经性听力损失和发育迟缓有关。通过对多个家族进行研究，我们将这种疾病定位到2号染色体的2q23.3-31.1区域，并在6个患有唐纳-巴罗综合征的家族和1个患有面-眼-耳-肾综合征的家族中鉴定出LRP2基因突变。LRP2编码巨膜蛋白，这是一种多配体摄取受体，可调节多种循环化合物的水平。这项研究揭示了一条具有潜在药理学治疗靶点的途径。
