Qualitative and quantitative analysis of FBN1 mRNA from 16 patients with Marfan Syndrome

BMC Medical Genetics

Table 1 FBN1 genotype, predicted effect, fibroblast FBN1 expression level, and patient characteristics

FBN1 nucleotide change	Protein change	Affected domain	In silico prediction^a	Type of mutation	FBN1 mRNA % of controls^b	Clinical phenotype^c
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.T6339A^d	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)

ISSN: 1471-2350