Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes
Kantarci, Sibel × Al-Gazali, Lihadh Hill, R Sean Donnai, Dian Black, Graeme C M Bieth, Eric Chassaing, Nicolas Lacombe, Didier Devriendt, Koenraad 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 #
Nature America, Inc.
Nature Genetics vol:39 issue:8 pages:957-959
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.