Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues
Open accessAbstract
Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues.
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Fibulin-1 mutations are associated with cognitive deficits in humans.
“Interestingly, fibulin-1 mutations are associated with cognitive deficits in the human and fibulin-2 mediates TGF-beta1 effects on adult neural stem cells50,51.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [50]
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A method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194 · see citing works
Human Protein Reference Database--2009 update
Prasad, T. S. K., Goel, R., Kandasamy, K., Keerthikumar, S., Kumar, S., Mathivanan, S., Telikicherla, D., Raju, R., Shafreen, R. B., Venugopal, A., et al. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn892 · Cited by 3,205 · see citing works
Stone, E. M., Lotery, A. J., Munier, F. L., Héon, E., Piguet, B., Guymer, R. H., Vandenburgh, K., Cousin, P., Nishimura, D. Y., Swiderski, R. E., et al. (1999) · Nature Genetics · doi:10.1038/9722 · Cited by 488 · see citing works
Missense Variations in the Fibulin 5 Gene and Age-Related Macular Degeneration
Stone, E. M., Braun, T. A., Russell, S. R., Kuehn, M. H., Lotery, A. J., Moore, P. A., Eastman, C. G., Casavant, T. L., & Sheffield, V. C. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040833 · Cited by 324 · see citing works
Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa
Loeys, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.18.2113 · Cited by 320 · see citing works
Structure and function of epidermal growth factor‐like regions in proteins
Appella, E., Weber, I. T., & Blasi, F. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)80690-2 · Cited by 314 · see citing works
Fibulin-4: A Novel Gene for an Autosomal Recessive Cutis Laxa Syndrome
Hucthagowder, V., Sausgruber, N., Kim, K. H., Angle, B., Marmorstein, L. Y., & Urbán, Z. (2006) · The American Journal of Human Genetics · doi:10.1086/504304 · Cited by 305 · see citing works
Fibulins: Multiple roles in matrix structures and tissue functions
de Vega, S., Iwamoto, T., & Yamada, Y. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-8632-6 · Cited by 270 · see citing works
Schultz, D. W., Klein, M. L., Humpert, A. J., Luzier, C. W., Persun, V., Schain, M. B., Mahan, A. E., Runckel, C., Cassera, M. A., Vittal, V., et al. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg348 · Cited by 191 · see citing works
Fibulin-1 is required for morphogenesis of neural crest-derived structures
Cooley, M. A., Kern, C. B., Fresco, V. M., Wessels, A., Thompson, R. P., McQuinn, T. C., Twal, W. O., Mjaatvedt, C. H., Drake, C. J., & Argraves, W. S. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.04.029 · Cited by 107 · see citing works
MMDB: 3D structures and macromolecular interactions
Madej, T., Addess, K. J., Fong, J. H., Geer, L. Y., Geer, R. C., Lanczycki, C. J., Liu, C., Lu, S., Marchler‐Bauer, A., Panchenko, A. R., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1162 · Cited by 107 · see citing works
Debeer, P., Schoenmakers, E. F. P. M., Twal, W. O., et al. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.2.98 · Cited by 106 · see citing works
Crystal Structure of Human Epidermal Growth Factor and Its Dimerization
Lü, H., Chai, J., Li, M., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102874200 · Cited by 87 · see citing works
Tran, H., VanDusen, W. J., & Argraves, W. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22600 · Cited by 71 · see citing works
Grossniklaus, H. E. (2004) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2004.10.036 · Cited by 63 · see citing works
Molecular evolution of the fibulins: Implications on the functionality of the elastic fibulins
Segade, F. (2010) · Gene · doi:10.1016/j.gene.2010.05.003 · Cited by 45 · see citing works
Distinct regions within fibulin-1D modulate interactions with hemicentin
Muriel, J. M., Dong, C., & Vogel, B. E. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.08.007 · Cited by 11 · see citing works
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- Authors
- Bohlega, S., Al-Ajlan, H., & Al-Saif, A.
- Affiliations
- King Faisal Specialist Hospital & Research Centre (SA)
- National Institutes of Health (US)
- Corresponding author
- Al-Saif, Amr
- ORCID
- Bohlega, Saeed
- Venue
- European Journal of Human Genetics
- Published
- 2013-10-02
- Volume
- 22
- Issue
- 5
- Pages
- 640-643
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- PMC
- PMC3992572
- OpenAlex
- W1976550985
- Cited by
- 14
- References
- 17
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- fibulin-1, missense mutations, disulfide bonds, extracellular matrix proteins, elastic fibers, basement membrane, syndactyly, cryptorchidism, delayed motor development, intellectual disability, brain atrophy, connective tissue diseases, central nervous system development, consanguineous family, homozygosity mapping, exome sequencing
- MeSH terms
- Brain, Calcium-Binding Proteins, Central Nervous System Diseases, Child, Preschool, Chromosome Mapping, Connective Tissue Diseases, DNA Mutational Analysis, Female, Homozygote, Humans, Infant, Magnetic Resonance Imaging, Male, Models, Molecular, Mutation, Pedigree, Protein Conformation, Spinal Cord, Syndrome, Amino Acid Substitution, High-Throughput Nucleotide Sequencing, Exome
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