LRP4 mutations alter Wnt/β-catenin signaling and cause limb and kidney malformations in Cenani–Lenz syndrome
Open accessAbstract
Cenani-Lenz syndrome (CLS) is an autosomal-recessive congenital disorder affecting distal limb development. It is characterized mainly by syndactyly and/or oligodactyly and is now shown to be commonly associated with kidney anomalies. We used a homozygosity-mapping approach to map the CLS1 locus to chromosome 11p11.2-q13.1. By sequencing candidate genes, we identified recessive LRP4 mutations in 12 families with CLS. LRP4 belongs to the low-density lipoprotein (LDL) receptor-related proteins (LRPs), which are essential for various developmental processes. LRP4 is known to antagonize LRP6-mediated activation of canonical Wnt signaling, a function that is lost by the identified mutations. Our findings increase the spectrum of congenital anomalies associated with abnormal lipoprotein receptor-dependent signaling.
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Lrp4 is the gene mutated in Cenani-Lenz syndrome.
“Lrp4 is more commonly known as the gene defective in Cenani-Lenz syndrome [83–86]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [86]
Lrp4 is not absolutely required for neuromuscular junction development in humans and cattle.
“but intriguingly not in humans [86] and cattle [91]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [86]
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References 31 · Cited by 171
- Authors
- Li, Y., Pawlik, B., Elcioglu, N., Aglan, M., Kayserili, H., Yigit, G., Percin, F., Goodman, F., Nürnberg, G., Cenani, A., Urquhart, J., Chung, B.-D., Ismail, S., Amr, K., Aslanger, A. D., Becker, C., Netzer, C., Scambler, P., Eyaid, W., Hamamy, H., Clayton-Smith, J., Hennekam, R., Nürnberg, P., Herz, J., Temtamy, S. A., & Wollnik, B.
- Affiliations
- University of Cologne (DE)
- Marmara Üniversitesi Eğitim ve Araştırma Hastanesi (TR)
- National Research Centre (EG)
- Istanbul University (TR)
- Great Ormond Street Hospital (GB)
- Manchester Academic Health Science Centre (GB)
- King Abdulaziz Medical City (SA)
- University Hospital of Geneva (CH)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Wollnik, Bernd
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 86
- Issue
- 5
- Pages
- 696-706
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2869043
- OpenAlex
- W2171967326
- Cited by
- 171
- References
- 31
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 11 · 2021: 12 · 2020: 6 · 2019: 9 · 2018: 8 · 2017: 12 · 2016: 10 · 2015: 15 · 2014: 20 · 2013: 11 · 2012: 13
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dspace Repository (Marmara Üniversitesi) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- GRO (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- National Institutes of Health
- American Health Assistance Foundation
- Alexander von Humboldt-Stiftung
- Deutsche Forschungsgemeinschaft (NE826/3-2)
- Bundesministerium für Bildung und Forschung (01GM0880)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- LRP4, Wnt/β-catenin signaling, LRP6, limb malformations, syndactyly, oligodactyly, renal anomalies, congenital malformations, homozygosity mapping, chromosome 11, autosomal recessive disorder
- MeSH terms
- Humans, Kidney, Kidney Diseases, Mutation, Oncogenes, Receptors, LDL, Syndactyly, Syndrome, Signal Transduction, Limb Deformities, Congenital, LDL-Receptor Related Proteins, beta Catenin, Low Density Lipoprotein Receptor-Related Protein-6
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