title: 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.affiliation: Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Simches Research Building, 185 Cambridge St., Boston, Massachusetts 02114 USA.
authors.forename: Sibel
authors.initials: S
authors.lastname: Kantarci
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
authors.forename: R Sean
authors.initials: RS
authors.lastname: Hill
authors.forename: Dian
authors.initials: D
authors.lastname: Donnai
authors.forename: Graeme C M
authors.initials: GC
authors.lastname: Black
authors.forename: Eric
authors.initials: E
authors.lastname: Bieth
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Ahmad
authors.initials: A
authors.lastname: Teebi
authors.forename: Maria
authors.initials: M
authors.lastname: Loscertales
authors.forename: Caroline
authors.initials: C
authors.lastname: Robson
authors.forename: Tianming
authors.initials: T
authors.lastname: Liu
authors.forename: David T
authors.initials: DT
authors.lastname: MacLaughlin
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Noonan
authors.forename: Meaghan K
authors.initials: MK
authors.lastname: Russell
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Pober
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D061085:Agenesis of Corpus Callosum; D002889:Chromosomes, Human, Pair 2; D019465:Craniofacial Abnormalities / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000235:genetics; D005190:Family; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006548:Hernia, Diaphragmatic / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics*; D009154:Mutation; D013577:Syndrome
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2