Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes.

Abstract

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.

• Authors: Sibel Kantarci, Lihadh Al-Gazali, R Sean Hill, Dian Donnai, Graeme C M Black, Eric Bieth, Nicolas Chassaing, Didier Lacombe, Koen Devriendt, Ahmad Teebi, Maria Loscertales, Caroline Robson, Tianming Liu, David T MacLaughlin, Kristin M Noonan, Meaghan K Russell, Christopher A Walsh, Patricia K Donahoe, Barbara R Pober
• Journal: Nature genetics (Nat Genet) Vol. 39 Issue 8 Pg. 957-9 (Aug 2007) ISSN: 1061-4036 [Print] United States
• PMID: 17632512 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Low Density Lipoprotein Receptor-Related Protein-2

Topics

• Abnormalities, Multiple (genetics)
• Agenesis of Corpus Callosum
• Chromosomes, Human, Pair 2
• Craniofacial Abnormalities (genetics)
• Eye Diseases, Hereditary (genetics)
• Family
• Hearing Loss, Sensorineural (genetics)
• Hernia, Diaphragmatic (genetics)
• Humans
• Kidney (abnormalities)
• Low Density Lipoprotein Receptor-Related Protein-2 (genetics)
• Mutation
• Syndrome