Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q

Carmel Toomes; Helen M. Bottomley; Richard M. Jackson; Katherine V. Towns; Sheila Scott; David A. Mackey; Jamie E. Craig; Li Jiang; Zhenglin Yang; Richard Trembath; Geoffrey Woodruff; Cheryl Y. Gregory-Evans; Kevin Gregory-Evans; Michael J. Parker; Graeme C M Black; Louise M. Downey; Kang Zhang; Chris F. Inglehearn

doi:10.1086/383202

Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q

Carmel Toomes, Helen M. Bottomley, Richard M. Jackson, Katherine V. Towns, Sheila Scott, David A. Mackey, Jamie E. Craig, Li Jiang, Zhenglin Yang, Richard Trembath, Geoffrey Woodruff, Cheryl Y. Gregory-Evans, Kevin Gregory-Evans, Michael J. Parker, Graeme C M Black, Louise M. Downey, Kang Zhang, Chris F. Inglehearn

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	721-730
Number of pages	9
Journal	American Journal of Human Genetics
Volume	74
Issue number	4
DOIs	https://doi.org/10.1086/383202
Publication status	Published - Apr 2004

Keywords

Amino Acid Sequence
Base Sequence
genetics: Chromosomes, Human, Pair 11
genetics: Exons
Female
Humans
genetics: Introns
Male
Models, Molecular
Molecular Sequence Data
genetics: Mutation
Pedigree
Polymorphism, Single-Stranded Conformational
Protein Structure, Tertiary
genetics: Proteins
chemistry: Receptors, LDL
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
genetics: Retinal Diseases

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10.1086/383202

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Toomes, C., Bottomley, H. M., Jackson, R. M., Towns, K. V., Scott, S., Mackey, D. A., Craig, J. E., Jiang, L., Yang, Z., Trembath, R., Woodruff, G., Gregory-Evans, C. Y., Gregory-Evans, K., Parker, M. J., Black, G. C. M., Downey, L. M., Zhang, K., & Inglehearn, C. F. (2004). Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q. American Journal of Human Genetics, 74(4), 721-730. https://doi.org/10.1086/383202

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title = "Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q",

abstract = "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.",

keywords = "Amino Acid Sequence, Base Sequence, genetics: Chromosomes, Human, Pair 11, genetics: Exons, Female, Humans, genetics: Introns, Male, Models, Molecular, Molecular Sequence Data, genetics: Mutation, Pedigree, Polymorphism, Single-Stranded Conformational, Protein Structure, Tertiary, genetics: Proteins, chemistry: Receptors, LDL, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., genetics: Retinal Diseases",

author = "Carmel Toomes and Bottomley, {Helen M.} and Jackson, {Richard M.} and Towns, {Katherine V.} and Sheila Scott and Mackey, {David A.} and Craig, {Jamie E.} and Li Jiang and Zhenglin Yang and Richard Trembath and Geoffrey Woodruff and Gregory-Evans, {Cheryl Y.} and Kevin Gregory-Evans and Parker, {Michael J.} and Black, {Graeme C M} and Downey, {Louise M.} and Kang Zhang and Inglehearn, {Chris F.}",

year = "2004",

month = apr,

doi = "10.1086/383202",

language = "English",

volume = "74",

pages = "721--730",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "4",

}

Toomes, C, Bottomley, HM, Jackson, RM, Towns, KV, Scott, S, Mackey, DA, Craig, JE, Jiang, L, Yang, Z, Trembath, R, Woodruff, G, Gregory-Evans, CY, Gregory-Evans, K, Parker, MJ, Black, GCM, Downey, LM, Zhang, K & Inglehearn, CF 2004, 'Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q', American Journal of Human Genetics, vol. 74, no. 4, pp. 721-730. https://doi.org/10.1086/383202

TY - JOUR

T1 - Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q

AU - Toomes, Carmel

AU - Bottomley, Helen M.

AU - Jackson, Richard M.

AU - Towns, Katherine V.

AU - Scott, Sheila

AU - Mackey, David A.

AU - Craig, Jamie E.

AU - Jiang, Li

AU - Yang, Zhenglin

AU - Trembath, Richard

AU - Woodruff, Geoffrey

AU - Gregory-Evans, Cheryl Y.

AU - Gregory-Evans, Kevin

AU - Parker, Michael J.

AU - Black, Graeme C M

AU - Downey, Louise M.

AU - Zhang, Kang

AU - Inglehearn, Chris F.

PY - 2004/4

Y1 - 2004/4

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Base Sequence

KW - genetics: Chromosomes, Human, Pair 11

KW - genetics: Exons

KW - Female

KW - Humans

KW - genetics: Introns

KW - Male

KW - Models, Molecular

KW - Molecular Sequence Data

KW - genetics: Mutation

KW - Pedigree

KW - Polymorphism, Single-Stranded Conformational

KW - Protein Structure, Tertiary

KW - genetics: Proteins

KW - chemistry: Receptors, LDL

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, P.H.S.

KW - genetics: Retinal Diseases

U2 - 10.1086/383202

DO - 10.1086/383202

M3 - Article

SN - 0002-9297

VL - 74

SP - 721

EP - 730

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 4

ER -

Mutations in LRP5 or FZD4 Underlie the Common Familial Exudative Vitreoretinopathy Locus on Chromosome 11q

Abstract

Keywords

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