Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes.
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.
Kantarci
Sibel
S
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Simches Research Building, 185 Cambridge St., Boston, Massachusetts 02114 USA.
Al-Gazali
Lihadh
L
Hill
R Sean
RS
Donnai
Dian
D
Black
Graeme C M
GC
Bieth
Eric
E
Chassaing
Nicolas
N
Lacombe
Didier
D
Devriendt
Koen
K
Teebi
Ahmad
A
Loscertales
Maria
M
Robson
Caroline
C
Liu
Tianming
T
MacLaughlin
David T
DT
Noonan
Kristin M
KM
Russell
Meaghan K
MK
Walsh
Christopher A
CA
Donahoe
Patricia K
PK
Pober
Barbara R
BR
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
D026561:Low Density Lipoprotein Receptor-Related Protein-2