Table 1.
FBN1 genotype, predicted effect, fibroblast FBN1 expression level, and patient characteristics
| FBN1 nucleotide change | Protein change | Affected domain | In silico predictiona | Type of mutation | FBN1 mRNA % of controlsb | Clinical phenotypec |
|---|---|---|---|---|---|---|
| c.G629A | p.Cys210Tyr | Hybrid | Probably damaging | Missense | 120 ± 35 | DOsp |
| c.G1027A | p.Gly343Arg | TGF-β1 | Possibly damaging | Missense | 219 ± 35 | Dos |
| c.G2447T | p.Cys816Phe | cbEGF9 | Probably damaging | Missense | 212 ± 52 | DOCsi |
| c.T2848C | p.Cys950Arg | cbEGF10 | Probably damaging | Missense | 100 ± 16 | DOCsi |
| c.T4348G | p.Cys1450Gly | cbEGF21 | Probably | Missense | 169 ± 26 | DOoCcSsi |
| c.T5866C | p.Cys1956Arg | cbEGF29 | damaging | Missense | 141 ± 24 | DOoSi |
| c.G6388A | p.Glu2130Lys | cbEGF32 | Possibly damaging | Missense | 119 ± 27 | DOSsip |
| c.G7094A | p.Cys2365Tyr | TGF-β7 | Possibly damaging | Missense | 109 ± 18 | DOS |
| Probably damaging | ||||||
| c.4269_4270delAC | p.Pro1424Argfs*6 | cbEGF20 | Fs, introducing | PTC (fs) | 88 ± 23 | DCcSi |
| c.5559delT | p.Gln1854Lysfs*39 | cbEGF27 | Fs, introducing | PTC (fs) | 75 ± 19 | DCcs |
| c.T6339Ad | p.Tyr2113X | TGF-β6 | PTC skip of exon 25 | PTC (fs) | 53 ± 8 | Ds |
| c.3083-2A > G | - | Intronic | Skip of exon 25 | Splice site | 51 ± 10 | DOoCcSs |
| c.4211-1G > A | - | Intronic | Skip of exon 34 | Splice site | 59 ± 11 | DOoCcspi |
| c.4817-2delA | p.Ile1607_Asp1648del | Intronic | Skip of exon 39 | Splice site | 80 ± 16 | DOCcsi |
| c.4942 + 2 T > C | - | Intronic | Skip of exon 39 | Splice site | 72 ± 12 | DOoCcSsp |
| c.A4925G | p.Thr1643_Asp1648del | cbEGF23 | CSS | Splice site (CSS) | 91 ± 17 | DOosi |
Exons are numbered according to the reference sequence GenBank NM_000138.4. cb, calcium binding
EGF, epidermal growth factor, fs frame shift, PTC premature termination codon, TGF transforming growth factor, CSS cryptic splice site
a In silico prediction of mutations was obtained using ALAMUT prediction algorithms
bMean FBN1 mRNA expression levels in five parallel wells of fibroblasts from MFS patients compared to controls (n = 6) ± SD. The level in controls was assigned as 100 %
cAffection of organ systems is given according to the original Ghent nosology for the diagnosis MFS. Dura mater: Major criterion: D. Ocular system: Major criterion: O, Minor manifestations: o. Cardiovascular system: Major criteria: C, Minor criteria: c. Skeletal system: Major manifestations: S, minor manifestations: s. Skin and integument: Minor criteria implying involvement: i, Pulmonary system: Minor criteria implying involvement: p. dThe mutation was contained in the UMD-FBN1 database (recurrent mutation)