Fibrillin 1 (FBN1)

FBN; MASS; MFS1; OCTD; SGS; Asprosin

SPN	W217
HGNC	3603
MGI	95489
PubMed	8541880
RGD	620908
UniProt	P35555
Wiki	FBN1

Fibrillin-1 is a major component of the microfibrils that form a sheath surrounding the amorphous elastin. It is believed that the microfibrils are composed of end-to-end polymers of fibrillin. To date, 3 forms of fibrillin have been described. The fibrillin-1 protein was isolated by Engvall in 1986, and mutations in the gene have been linked to the Marfan syndrome. At present more than 100 different mutations have been described. Trask et al. (1999) found that human FIB1 and FIB2 homodimerized via an N-terminal region and that the interaction was stabilized by disulphide bonds. Dimer formation occurred intracellularly, suggesting that the process of fibrillin aggregation initiates early after biosynthesis of the molecules.

Asprosin is generated from the gene FBN1 (amino acid residues 2732–2871), which also generates fibrillin.

Reference

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Nature 352:334-337(1991) [PubMed] [Europe PMC] [Abstract]

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Cell 85:597-605(1996) [PubMed] [Europe PMC] [Abstract]

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Hum. Mol. Genet. 3:373-375(1994) [PubMed] [Europe PMC] [Abstract]

"An extra cysteine in one of the non-calcium-binding epidermal growth factor-like motifs of the FBN1 polypeptide is connected to a novel variant of Marfan syndrome."
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"A new missense mutation of fibrillin in a patient with Marfan syndrome."
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"A Gly1127Ser mutation in an EGF-like domain of the fibrillin-1 gene is a risk factor for ascending aortic aneurysm and dissection."
Am. J. Hum. Genet. 56:1287-1296(1995) [PubMed] [Europe PMC] [Abstract]

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Am. J. Hum. Genet. 57:8-21(1995) [PubMed] [Europe PMC] [Abstract]

"The phenotypic continuum associated with FBN1 mutations includes the Shprintzen-Goldberg syndrome."
Am. J. Hum. Genet. 57:A211-A211(1995)

"A mutation in FBN1 disrupts profibrillin processing and results in isolated skeletal features of the Marfan syndrome."
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"Delineation of the Marfan phenotype associated with mutations in exons 23-32 of the FBN1 gene."
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J. Med. Genet. 33:665-671(1996) [PubMed] [Europe PMC] [Abstract]

"A novel de novo mutation in exon 14 of the fibrillin-1 gene associated with delayed secretion of fibrillin in a patient with a mild Marfan phenotype."
Hum. Genet. 100:195-200(1997) [PubMed] [Europe PMC] [Abstract]

"The pathogenicity of the Pro1148Ala substitution in the FBN1 gene: causing or predisposing to Marfan syndrome and aortic aneurysm, or clinically innocent?"
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"P1148A in fibrillin-1 is not a mutation leading to Shprintzen-Goldberg syndrome."
Hum. Mutat. 10:326-327(1997) [PubMed] [Europe PMC] [Abstract]

"P1148A in fibrillin-1 is not a mutation anymore."
Nat. Genet. 15:12-12(1997) [PubMed] [Europe PMC] [Abstract]

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Am. J. Hum. Genet. 63:1703-1711(1998) [PubMed] [Europe PMC] [Abstract]

"Correlation of a recurrent FBN1 mutation (R122C) with an atypical familial Marfan syndrome phenotype."
Hum. Mutat. Suppl. 1:S198-S200(1998) [PubMed] [Europe PMC] [Abstract]

"A novel mutation in the neonatal region of the fibrillin (FBN) 1 gene associated with a classical phenotype of Marfan syndrome (MfS)."
Hum. Mutat. 12:137-137(1998) [PubMed] [Europe PMC] [Abstract]

"Demonstration of the recurrence of Marfan-like skeletal and cardiovascular manifestations due to germline mosaicism for an FBN1 mutation."
Am. J. Hum. Genet. 65:917-921(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of 9 novel FBN1 mutations in German patients with Marfan syndrome."
Hum. Mutat. 14:181-181(1999) [PubMed] [Europe PMC] [Abstract]

"Genotype and phenotype analysis of 171 patients referred for molecular study of the fibrillin-1 gene FBN1 because of suspected Marfan syndrome."
Arch. Intern. Med. 161:2447-2454(2001) [PubMed] [Europe PMC] [Abstract]

"TGGE screening of the entire FBN1 coding sequence in 126 individuals with Marfan syndrome and related fibrillinopathies."
Hum. Mutat. 20:197-208(2002) [PubMed] [Europe PMC] [Abstract]

"Sensitivity of conformation sensitive gel electrophoresis in detecting mutations in Marfan syndrome and related conditions."
J. Med. Genet. 39:34-41(2002) [PubMed] [Europe PMC] [Abstract]

"In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome."
J. Med. Genet. 40:34-36(2003) [PubMed] [Europe PMC] [Abstract]

"Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy."
Hum. Mutat. 23:99-99(2004) [PubMed] [Europe PMC] [Abstract]

"Consequences of cysteine mutations in calcium-binding epidermal growth factor modules of fibrillin-1."
J. Biol. Chem. 279:32924-32931(2004) [PubMed] [Europe PMC] [Abstract]

"Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies."
Hum. Mutat. 26:494-494(2005) [PubMed] [Europe PMC] [Abstract]

"Identification of 29 novel and nine recurrent fibrillin-1 (FBN1) mutations and genotype-phenotype correlations in 76 patients with Marfan syndrome."
Hum. Mutat. 26:529-539(2005) [PubMed] [Europe PMC] [Abstract]

"Central nervous system abnormalities in two cases with neonatal Marfan syndrome with novel mutations in the fibrillin-1 gene."
Am. J. Med. Genet. A 152:2409-2412(2010) [PubMed] [Europe PMC] [Abstract]

"A Japanese-specific allele in the GALNT11 gene."
Leg. Med. 12:208-211(2010) [PubMed] [Europe PMC] [Abstract]

"Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome."
Sci. Transl. Med. 2:23RA20-23RA20(2010) [PubMed] [Europe PMC] [Abstract]

"Mutations in the TGFbeta binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias."
Am. J. Hum. Genet. 89:7-14(2011) [PubMed] [Europe PMC] [Abstract]

"Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes."
Hum. Mutat. 32:1053-1062(2011) [PubMed] [Europe PMC] [Abstract]