Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q.
Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Autosomal dominant FEVR is genetically heterogeneous, but its principal locus, EVR1, is on chromosome 11q13-q23. The gene encoding the Wnt receptor frizzled-4 (FZD4) was recently reported to be the EVR1 gene, but our mutation screen revealed fewer patients harboring mutations than expected. Here, we describe mutations in a second gene at the EVR1 locus, low-density-lipoprotein receptor-related protein 5 (LRP5), a Wnt coreceptor. This finding further underlines the significance of Wnt signaling in the vascularization of the eye and highlights the potential dangers of using multiple families to refine genetic intervals in gene-identification studies.
Toomes
Carmel
C
Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom. c.toomes@leeds.ac.uk
Bottomley
Helen M
HM
Jackson
Richard M
RM
Towns
Katherine V
KV
Scott
Sheila
S
Mackey
David A
DA
Craig
Jamie E
JE
Jiang
Li
L
Yang
Zhenglin
Z
Trembath
Richard
R
Woodruff
Geoffrey
G
Gregory-Evans
Cheryl Y
CY
Gregory-Evans
Kevin
K
Parker
Michael J
MJ
Black
Graeme C M
GC
Downey
Louise M
LM
Zhang
Kang
K
Inglehearn
Chris F
CF
D000595:Amino Acid Sequence; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D051157:Frizzled Receptors; D006801:Humans; D007438:Introns / Q000235:genetics; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL / Q000737:chemistry / Q000235:genetics*; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology
C402930:FZD4 protein, human; D051157:Frizzled Receptors; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D011506:Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011973:Receptors, LDL