Alternative titles; symbols
HGNC Approved Gene Symbol: FBLN5
Cytogenetic location: 14q32.12 Genomic coordinates (GRCh38) : 14:91,869,411-91,947,694 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 14q32.12 | ?Cutis laxa, autosomal dominant 2 | 614434 | Autosomal dominant | 3 |
| Charcot-Marie-Tooth disease, demyelinating, type 1H | 619764 | Autosomal dominant | 3 | |
| Cutis laxa, autosomal recessive, type IA | 219100 | Autosomal recessive | 3 | |
| Macular degeneration, age-related, 3 | 608895 | Autosomal dominant | 3 |
Members of the fibulin family of proteins, like FBLN5, are extracellular matrix proteins characterized by tandem arrays of EGF (131530)-like domains and a C-terminal fibulin (see FBLN1; 135820)-type module (Kobayashi et al., 2007).
Using a cDNA probe derived from signal sequence trap screening of mouse embryonic heart, EST database screening, and 5-prime RACE, Nakamura et al. (1999) obtained a cDNA for fibulin-5 (FBLN5), which they called DANCE (for developmental arteries and neural crest EGF-like). The FBLN5 cDNA encodes a deduced 448-amino acid secreted protein with a molecular mass of 66 kD. Its amino acid sequence is 94% identical to that of the mouse Fbln5 protein. It contains 6 calcium-binding EGF-like domains, one of which contains an RGD motif. Northern blot analysis revealed a major transcript of 2.6 kb that is expressed predominantly in heart, ovary, and colon but also in kidney, pancreas, testis, lung, and placenta. FBLN5 is not detectable in brain, liver, thymus, prostate, or peripheral blood leukocytes. FBLN5 is prominently expressed in developing arteries; in adult vessels, its expression is largely diminished but is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells.
Using radioimmunoassays, Kobayashi et al. (2007) found variable Fbln5 expression in all 14 mouse tissues examined, with highest expression in aorta and lung, and lowest expression in kidney, brain, and thymus. Immunohistochemical analysis localized Fbln5 in perichondrium of developing bone in day-15 mouse embryos and in blood vessel wall, basement membrane, and parabronchial area of the large airway in day-14 mouse embryos. Electron microscopy after rotary shadowing revealed that recombinant mouse Fbln5, like Fbln3 (EFEMP1; 601548) and Fbln4 (604633), appeared as a 20-nm rod with a globular domain at one end, which represented the N-terminal EGF modules.
By FISH, Nakamura et al. (1999) mapped the FBLN5 gene to chromosome 14q32.1. By FISH and radiation hybrid analysis, Kowal et al. (1999) mapped the FBLN5 gene to 14q31.
Nakamura et al. (1999) showed that FBLN5 promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. The authors suggested that FBLN5 is a novel vascular ligand for integrin receptors and may play a role in vascular development and remodeling.
Mullins et al. (2007) localized the fibulin-5 protein to Bruch membrane and to the intercapillary pillars of the choriocapillaris in normal human donor eyes. In eyes with age-related macular degeneration (ARMD3; 608895), they localized the protein to pathologic basal deposits beneath the retinal pigment epithelium (RPE) as well as in some small drusen. Mullins et al. (2007) suggested that fibulin-5 may promote extracellular deposit formation in macular degeneration.
Kobayashi et al. (2007) found that mouse Fbln3 and Fbln4 and both mouse and human FBLN5 were secreted into the culture media of transfected HEK293 cells. Solid-phase binding assays showed that these proteins bound differentially to extracellular proteins. Mouse Fbln5 bound to tropoelastin (ELN; 130160) and weakly to collagen XV (see 120325)-derived endostatin, but not to fibronectin (135600) or most basement membrane proteins examined.
Autosomal Recessive Cutis Laxa
Hereditary cutis laxa comprises a heterogeneous group of connective tissue disorders characterized by loose skin and variable systemic involvement. The phenotypic abnormalities observed in a fibulin-5 knockout mouse model by Nakamura et al. (2002) are reminiscent of human autosomal recessive cutis laxa type I (ARCL1A; 219100). Both share cutis laxa, lung emphysema, and arterial involvement. Loeys et al. (2002) studied a large consanguineous Turkish family with 4 patients affected by autosomal recessive cutis laxa type I, originally described by Van Maldergem et al. (1988), and demonstrated the presence of a homozygous missense mutation in the FBLN5 gene, resulting in a ser227-to-pro (S227P; 604580.0001) substitution.
Hu et al. (2006) analyzed 2 disease-causing missense substitutions in fibulin-5, C217R (604580.0010) and S227P, and found evidence for misfolding, decreased secretion, and reduced interaction with elastin and fibrillin-1, resulting in impaired elastic fiber development. These findings supported the hypothesis that fibulin-5 is necessary for elastic fiber formation by facilitating the deposition of elastin onto a microfibrillar scaffold via direct molecular interactions.
Callewaert et al. (2013) analyzed the FBLN4 (604633), FBLN5, and LTBP4 (604710) genes in 12 families with type I ARCL and identified homozygous mutations in the FLBN5 gene in 2 families (604580.0010 and 604580.0011). Homozygous or compound heterozygous mutations in LTBP4 were identified in 9 families (see, e.g., 604710.0005-604710.0008). No mutations were found in the FBLN4 gene, and no mutations were detected in 1 family in which the proband had cutis laxa and bladder diverticula without obvious emphysema. Callewaert et al. (2013) noted that the FBLN5 and LTBP4 mutations caused a very similar phenotype associated with severe pulmonary emphysema, in the absence of vascular tortuosity or aneurysms. Gastrointestinal and genitourinary tract involvement seemed to be more severe in patients with LTBP4 mutations.
Autosomal Dominant Cutis Laxa
In a patient with autosomal dominant cutis laxa (ADCL2; 614434), Markova et al. (2003) identified a 22-kb tandem duplication in the FBLN5 gene, resulting in a 483-bp duplication (604580.0002).
Age-Related Macular Degeneration 3
Stone et al. (2004) studied 402 patients with age-related macular degeneration (ARMD3; 608895) and identified 7 different mutations in the FBLN5 gene (604580.0003-604580.0009) that were not found in any of 429 controls (p = 0.006). Each of the 7 patients had small circular drusen, commonly referred to as basal laminar or cuticular drusen. All of the patients were examined in a retina clinic.
Lotery et al. (2006) investigated the role of fibulin-5 in ARMD using 2 European cohorts of 805 ARMD patients and 279 controls and by determining the functional effects of the missense mutations on expression of the FBLN5 gene. They found 2 novel sequence changes in ARMD patients that were absent in controls and expressed these and the other 9 previously reported FBLN5 mutations associated with ARMD and 2 associated with autosomal recessive cutis laxa. Fibulin-5 secretion was significantly reduced (p less than 0.001) for 4 ARMD missense mutations and 2 cutis laxa mutations. These results suggested that some missense mutations associated with ARMD lead to decreased fibulin-5 secretion with a possible corresponding reduction in elastinogenesis. The studies further demonstrated that FBLN5 mutations can be associated with different phenotypes of ARMD (not limited to the previously described cuticular drusen type). FBLN5 ARMD can be a cause of choroidal neovascularization in the absence of drusen.
Demyelinating Charcot-Marie-Tooth disease, Type 1H
In affected members of 3 families with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011) identified 3 different heterozygous missense mutations in the FBLN5 gene (604580.0012-604580.0014). Functional studies of the variants were not performed.
Safka Brozkova et al. (2013) identified a heterozygous missense mutation in the FBLN5 gene (R373C; 604580.0012) in affected members of a Czech family with CMT1H. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family.
In 3 affected members spanning 3 generations of a Chinese family with CMT1H, Cheng et al. (2017) identified a heterozygous R373C mutation (604580.0012) in the FBLN5 gene.
In affected members of 19 families with CMT1H, some of whom had previously been reported, Safka Brozkova et al. (2020) identified 3 different heterozygous missense mutations in the FBLN5 gene. R373C (604580.0012) was the most common mutation, occurring in 15 families of Austrian, Czech, and French origin. Three families of Czech or German origin carried a heterozygous R331H mutation (604580.0015), and 1 French family carried a D329V mutation (604580.0016). The mutations, which were detected by Sanger sequencing, multigene panel sequencing, or whole-exome sequencing, segregated with the disorder in families from whom DNA was available for the affected members. Functional studies of the variants were not performed, but they were either absent from or found only once in the gnomAD database.
Yanagisawa et al. (2002) generated mice deficient in fibulin-5 by targeted disruption. Homozygous mutant mice were viable and appeared indistinguishable from wildtype littermates during the first 4 weeks except that slight looseness of the skin was noticeable by weaning. By approximately 50 days of age homozygous mutant mice showed lax skin, which progressed with age. The lungs of homozygous mutant mice were expanded and contained dilated alveoli, which were most severe in peripheral regions. There was tortuosity and elongation of the aorta, as well as elongation of the ductus arteriosus. The ascending aorta proximal to the aortic arch was elongated in fibulin-5 -/- mice, causing the brachiocephalic trunk and left common carotid artery to be juxtaposed. Elastin staining of skin showed a marked reduction of the elastic fiber network surrounding hair follicles. Enlargement of the distal airspaces of the lung was evident by 2 weeks of age in homozygous mutant mice. This phenotype progressed with age, leading to a severe emphysematous change with the formation of peripheral bullae in adult mice. Elastin staining showed that elastin (130160) at the tips of the secondary septae was fragmented and that the elastic fibers associated with the alveolar walls were short, thickened, and disrupted in 2-week-old homozygous mice when compared with wildtype littermates. Elastin staining of the aorta showed that elastic laminae in homozygous mutant mice were fragmented, the defect being more severe toward the adventitia. Despite the disorganized elastic laminae, there was no indication of aneurysms or dissections of the medial layers of aortae in fibulin-5 -/- mice. Other organs were normal. Disruption of the elastic laminae of vessels was evident as early as postnatal day 1, suggesting that the defect seen in the adult aorta of homozygous mutant mice was not the result of degradation of intact elastic laminae by activated inflammatory cells, but rather the consequence of an underlying developmental defect in the final organization of the elastic fibers in fibulin-5 -/- mice. Yanagisawa et al. (2002) performed solid-phase binding assays to assess the biochemical interaction of fibulin-5 with other extracellular matrix proteins. Fibulin-5 bound strongly to tropoelastin, and this binding was completely inhibited in the presence of EDTA, suggesting that fibulin-5 may use calcium-binding EGF-like motifs to bind to tropoelastin. Using immunogold labeling and electron microscopy, Yanagisawa et al. (2002) demonstrated that fibulin-5 protein is present along the surface of elastic lamina adjacent to the endothelial cell membrane, demonstrating that fibulin-5 is a surface component of elastic fibers in vivo.
Nakamura et al. (2002) independently generated fibulin-5 -/- mice. The phenotypic findings were similar to those described by Yanagisawa et al. (2002). They showed that the aorta, lung, and skin of fibulin-5 -/- mice contained fragmented elastin without an increase of elastase activity, indicating defective development of elastic fibers. Fibulin-5 interacts directly with elastic fibers in vitro, and serves as a ligand for cell surface integrins alpha-5/beta-3, alpha-5/beta-5 (see 193210), and alpha-9/beta-1 (see 603963) through its N-terminal domain. Nakamura et al. (2002) postulated that fibulin-5 may provide anchorage of elastic fibers to cells, thereby acting to stabilize and organize elastic fibers in the skin, lung, and vasculature.
Loeys et al. (2002) studied a large consanguineous Turkish family, originally described by Van Maldergem et al. (1988), in which 4 patients were affected by autosomal recessive cutis laxa type I (ARCL1A; 219100) and demonstrated homozygosity for a 998T-C transition in the FBLN5 gene. The mutation was predicted to result in a ser227-to-pro (S227P) substitution in the fourth cbEGF-like domain of fibulin-5 protein. Because serine is found in this position in mouse and rat fibulin-5 as well as in human fibulin-3, substitution for this amino acid may have important structural and functional consequences for normal elastogenesis.
Hu et al. (2006) showed that S227P mutant fibulin-5 is synthesized and secreted at a reduced rate compared to wildtype. The mutant also failed to be incorporated into elastic fibers by transfected rat lung fibroblasts. Purified recombinant S227P fibulin-5 showed reduced affinity for tropoelastin in solid-phase binding assays as well as impaired association with fibrillin-1 microfibrils; in addition, the mutant protein triggered an endoplasmic reticulum (ER) stress response, as indicated by strong colocalization of the mutant with folding chaperones in the ER and by increased rates of apoptosis in patient fibroblasts. Histologic analysis of patient skin sections showed a lack of fibulin-5 in the extracellular matrix and concomitant disorganization of dermal elastic fibers, and electron microscopy of patient elastic fibers showed a failure of elastin globules to fuse into a continuous elastic fiber core.
Markova et al. (2003) analyzed the expression of the elastin gene and the fibulin genes 1 through 5 in fibroblasts from 5 patients with cutis laxa (ADCL2; 614434). One patient was found to express both normal (2.2 kb) and mutant (2.7 kb) fibulin-5 mRNA transcripts. The larger transcript contained an internal duplication of 483 nucleotides, which resulted in the synthesis and secretion of a mutant fibulin-5 protein with 4 additional tandem calcium-binding epidermal growth factor-like motifs. The mutation arose from a 22-kb tandem gene duplication, encompassing the sequence from intron 4 to exon 9. No fibulin-5 or elastin mutations were detected in the other 4 patients.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.178G-C transversion in the FBLN5 gene, resulting in a val60-to-leu (V60L) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.212G-A transition in the FBLN5 gene, resulting in an arg71-to-gln (R71Q) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.259C-T transition in the FBLN5 gene, resulting in a pro87-to-ser (P87S) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.506T-C transition in the FBLN5 gene, resulting in an ile169-to-thr (I169T) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.1051C-T transition in the FBLN5 gene, resulting in an arg351-to-trp (R351W) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.1087G-A transition in the FBLN5 gene, resulting in an ala363-to-thr (A363T) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In a patient with age-related macular degeneration-3 and basal laminar drusen (ARMD3; 608895), Stone et al. (2004) identified a heterozygous c.1235G-A transition in the FBLN5 gene, resulting in a gly412-to-glu (G412E) substitution. This patient was 1 of 402 patients with age-related macular degeneration who were examined in a retina clinic.
In 3 affected sibs from a consanguineous Lebanese family with severe generalized cutis laxa (ARCL1A; 219100), Callewaert et al. (2013) identified homozygosity for a 649T-C transition in the FBLN5 gene, resulting in a cys217-to-arg (C217R) substitution at a highly conserved residue in the fourth calcium-binding EGF-like domain. The female proband died of pulmonary emphysema and bronchiolitis at 11 months of age; her 2 affected brothers had milder pulmonary emphysema. Other features in the 3 sibs included peripheral pulmonary artery stenosis, aortic valve stenosis and/or insufficiency, pyloric stenosis, and inguinal hernias. Callewaert et al. (2013) noted that the C217R had previously been identified by Claus et al. (2008) in another Lebanese family with cutis laxa.
In a 19-month-old girl from a consanguineous Algerian family with severe generalized cutis laxa with facial involvement (ARCL1A; 219100), Callewaert et al. (2013) identified homozygosity for a 1171G-T transversion in the FBLN5 gene, resulting in a glu391-to-ter (E391X) substitution in the FBLN-specific domain. The mutation was present in heterozygosity in the unaffected parents and an unaffected sister. The mother had had 2 spontaneous abortions and 2 older sisters and a brother with cutis laxa had died in infancy. The proband had a high and broad forehead, low and broad nasal bridge, beaked nose, large dysplastic ears, sagging cheeks, and everted lower lip. Other features included severe emphysema, normal cardiac status by echocardiography, photophobia, hypotonicity, and normal mental status.
In affected members of a large Austrian kindred (families A and B) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011), identified a heterozygous c.1117C-T transition (c.1117C-T, NM_006329.3) in exon 10 of the FBLN5 gene, resulting in an arg373-to-cys (R373C) substitution at a highly conserved residue in the fibulin-type C terminus. The mutation, which was found by analysis of protein coding genes within a region identified through linkage analysis, segregated with the disorder in the family and was not found in 317 control individuals or in the 1000 Genomes Project database. Functional studies of the variant were not performed. Nerve and muscle biopsy of 1 patient (B5) showed no obvious changes in the immunohistochemical staining patterns of FBLN5 and elastin, but skin biopsy from another patient (B9) showed mild changes in the structure and arrangement of FBLN5 and elastin; neither of these patients had clinical skin abnormalities or ARMD.
Safka Brozkova et al. (2013) identified a heterozygous R373C mutation in affected members of a Czech family with CMT1H. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, and was not found in the dbSNP (build 132) or Exome Variant Server databases. Functional studies of the variant were not performed. Haplotype analysis indicated that the mutation occurred independently from that in the family reported by Auer-Grumbach et al. (2011). None of the Czech patients had ARMD.
In 3 affected members spanning 3 generations of a Chinese family with CMT1H, Cheng et al. (2017) identified a heterozygous R373C mutation in the FBLN5 gene. The mutation, which was found by targeted next-generation sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, with evidence of variable expressivity and age-dependent penetrance. Functional studies of the variant were not performed.
Safka Brozkova et al. (2020) identified a heterozygous R373C mutation in the FBLN5 gene in affected members of 15 unrelated families from Austria, the Czech Republic, and France with CMT1H. The mutation, which was found by exome sequencing and segregated with the disorder in the families, was not present in the gnomAD database. Haplotype analysis indicated that some of the Czech families shared a similar haplotype, although others had independent mutational events. Functional studies of the variant were not performed. Three of the families had previously been reported.
In 5 affected members of a family (family C) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011) identified a heterozygous c.268G-A transition (c.268G-A, NM_006329.3) in exon 4 of the FBLN5 gene, resulting in a gly90-to-ser (G90S) substitution. The variant was not found in the 1000 Genomes Project database, in 517 control individuals, or in previous studies of 1,204 patients with ARMD or 766 control individuals. Two patients, 1 severely affected and 1 clinically asymptomatic, also carried a heterozygous A339T variant in the YARS gene (603623), but this variant did not segregate with the peripheral neuropathy in this family. Three affected family members had hyperelastic skin and 1 had ARMD. Functional studies of the variant were not performed. Skin biopsies from 2 patients with hyperelastic skin showed a marked increase in FBLN5 immunoreactivity, which was present as short plump fibers. An unrelated individual with sporadic occurrence of the disorder was also found to carry the G90S mutation.
In 2 members of a family (family D) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Auer-Grumbach et al. (2011) identified a heterozygous c.376G-A transition (rs61734479) in the FBLN5 gene, resulting in a val126-to-met (V126M) substitution at a conserved residue. The variant was also found in 2 of 317 supposed controls, both of whom were found to have peripheral neuropathy, as well as in 2 of 300 patients with age-related macular degeneration, 1 of whom had evidence of a peripheral neuropathy (patient data from Table 1). Functional studies of the variant were not performed.
In 4 patients from 3 unrelated families of Czech and German origin (CZ7, CZ8, and GE1) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Safka Brozkova et al. (2020) identified a heterozygous c.992G-A transition (c.992G-A, NM_006329.3) in the FBLN5 gene, resulting in an arg331-to-his (R331H) substitution at a highly conserved residue in the C-terminal domain. The mutation was present once in the gnomAD database. Segregation with the disorder was demonstrated in family CZ7. Functional studies of the variant and studies of patient cells were not performed.
In a French parent and offspring (family FR2) with demyelinating Charcot-Marie-Tooth disease, type 1H (CMT1H; 619764), Safka Brozkova et al. (2020) identified a heterozygous c.986A-T transversion (c.986A-T, NM_006329.3) in the FBLN5 gene, resulting in an asp329-to-val (D329V) substitution at a highly conserved residue in the C-terminal domain. The mutation, which was found by exome sequencing, was present once in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.
Auer-Grumbach, M., Weger, M., Fink-Puches, R., Papic, L., Frohlich, E., Auer-Grumbach, P., El Shabrawi-Caelen, L., Schabhuttl, M., Windpassinger, E., Senderek, J., Budka, H., Trajanoski, S., Janecke, A. R., Haas, A., Metze, D., Pieber, T. R., Guelly, C. Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin. Brain 134: 1839-1852, 2011. [PubMed: 21576112] [Full Text: https://doi.org/10.1093/brain/awr076]
Callewaert, B., Su, C.-T., Van Damme, T., Vlummens, P., Malfait, F., Vanakker, O., Schulz, B., Mac Neal, M., Davis, E. C., Lee, J. G. H., Salhi, A., Unger, S., and 16 others. Comprehensive clinical and molecular analysis of 12 families with type 1 recessive cutis laxa. Hum. Mutat. 34: 111-121, 2013. [PubMed: 22829427] [Full Text: https://doi.org/10.1002/humu.22165]
Cheng, S., Lv, H., Zhang, W., Wang, Z., Shi, X., Liang, W., Yuan, Y. Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation. Clin. Neuropath. 36: 171-177, 2017. [PubMed: 28332470] [Full Text: https://doi.org/10.5414/NP301011]
Claus, S., Fischer, J., Megarbane, H., Megarbane, A., Jobard, F., Debret, R., Peyrol, S., Saker, S., Devillers, M., Sommer, P., Damour, O. A p.C217R mutation in fibulin-5 from cutis laxa patients is associated with incomplete extracellular matrix formation in a skin equivalent model. J. Invest. Derm. 128: 1442-1450, 2008. [PubMed: 18185537] [Full Text: https://doi.org/10.1038/sj.jid.5701211]
Hu, Q., Loeys, B. L., Coucke, P. J., De Paepe, A., Mecham, R. P., Choi, J., Davis, E. C., Urban, Z. Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa. Hum. Molec. Genet. 15: 3379-3386, 2006. [PubMed: 17035250] [Full Text: https://doi.org/10.1093/hmg/ddl414]
Kobayashi, N., Kostka, G., Garbe, J. H. O., Keene, D. R., Bachinger, H. P., Hanisch, F.-G., Markova, D., Tsuda, T., Timpl, R., Chu, M.-L., Sasaki, T. A comparative analysis of the fibulin protein family: biochemical characterization, binding interactions, and tissue localization. J. Biol. Chem. 282: 11805-11816, 2007. [PubMed: 17324935] [Full Text: https://doi.org/10.1074/jbc.M611029200]
Kowal, R. C., Jolsin, J. M., Olson, E. N., Schultz, R. A. Assignment of fibulin-5 (FBLN5) to human chromosome 14q31 by in situ hybridization and radiation hybrid mapping. Cytogenet. Cell Genet. 87: 2-3, 1999. [PubMed: 10640802] [Full Text: https://doi.org/10.1159/000015382]
Loeys, B., van Maldergem, L., Mortier, G., Coucke, P., Gerniers, S., Naeyaert, J.-M., de Paepe, A. Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum. Molec. Genet. 11: 2113-2118, 2002. [PubMed: 12189163] [Full Text: https://doi.org/10.1093/hmg/11.18.2113]
Lotery, A. J., Baas, D., Ridley, C., Jones, R. P. O., Klaver, C. C. W., Stone, E., Nakamura, T., Luff, A., Griffiths, H., Wang, T., Bergen, A. A. B., Trump, D. Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa. Hum. Mutat. 27: 568-574, 2006. [PubMed: 16652333] [Full Text: https://doi.org/10.1002/humu.20344]
Markova, D., Zou, Y., Ringpfeil, F., Sasaki, T., Kostka, G., Timpl, R., Uitto, J., Chu, M.-L. Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene. Am. J. Hum. Genet. 72: 998-1004, 2003. [PubMed: 12618961] [Full Text: https://doi.org/10.1086/373940]
Mullins, R. F., Olvera, M. A., Clark, A. F., Stone, E. M. Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. Exp. Eye Res. 84: 378-380, 2007. [PubMed: 17109857] [Full Text: https://doi.org/10.1016/j.exer.2006.09.021]
Nakamura, T., Lozano, P. R., Ikeda, Y., Iwanaga, Y., Hinek, A., Minamisawa, S., Cheng, C.-F., Kobuke, K., Dalton, N., Takada, Y., Tashiro, K., Ross, J., Jr., Honjo, T., Chien, K. R. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature 415: 171-175, 2002. [PubMed: 11805835] [Full Text: https://doi.org/10.1038/415171a]
Nakamura, T., Ruiz-Lozano, P., Lindner, V., Yabe, D., Taniwaki, M., Furukawa, Y., Kobuke, K., Tashiro, K., Lu, Z., Andon, N. L., Schaub, R., Matsumori, A., Sasayama, S., Chien, K. R., Honjo, T. DANCE, a novel secreted RGD protein expressed in developing, atherosclerotic, and balloon-injured arteries. J. Biol. Chem. 274: 22476-22483, 1999. [PubMed: 10428823] [Full Text: https://doi.org/10.1074/jbc.274.32.22476]
Safka Brozkova, D., Lassuthova, P., Neupauerova, J., Krutova, M., Haberlova, J., Stejskal, D., Seeman, P. Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth type 1 neuropathy. (Letter) Brain 136: e232, 2013. Note: Electronic Article. [PubMed: 23328402] [Full Text: https://doi.org/10.1093/brain/aws333]
Safka Brozkova, D., Stojkovic, T., Haberlova, J., Mazanec, R., Windhager, R., Fernandes Rosenegger, P., Hacker, S., Zuchner, S., Kochanski, A., Leonard-Louis, S., Francou, B., Latour, P., Senderek, J., Seeman, P., Auer-Grumbach, M. Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations. Europ. J. Neurol. 27: 2568-2574, 2020. [PubMed: 32757322] [Full Text: https://doi.org/10.1111/ene.14463]
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. Missense variations in the fibulin 5 gene and age-related macular degeneration. New Eng. J. Med. 351: 346-353, 2004. [PubMed: 15269314] [Full Text: https://doi.org/10.1056/NEJMoa040833]
Van Maldergem, L., Vamos, E., Liebaers, I., Petit, P., Vandevelde, G., Simonis-Blumenfrucht, A., Bouffioux, R., Kulakowski, S., Hanquinet, S., Van Durme, P., Laporte, M., Ledoux-Corbusier, M. Severe congenital cutis laxa with pulmonary emphysema: a family with three affected sibs. Am. J. Med. Genet. 31: 455-464, 1988. [PubMed: 3232707] [Full Text: https://doi.org/10.1002/ajmg.1320310226]
Yanagisawa, H., Davis, E. C., Starcher, B. C., Ouchi, T., Yanagisawa, M., Richardson, J. A., Olson, E. N. Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivo. Nature 415: 168-171, 2002. [PubMed: 11805834] [Full Text: https://doi.org/10.1038/415168a]