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. 2008 Jan 9;111(7):3468–3478. doi: 10.1182/blood-2007-08-108068

Table 3.

Comparison of novel missense mutations in Spanish HA patients with previously reported replacements at the same or topologically equivalent positions

Mutation/equivalent mutations FVIII:C, % FVIII:Ag, % Clinical severity Inhibitor? Reference
p.Asp167Asn
    p.Asp167Tyr <1 1.6 Moderate† No Liu et al68
    p.Asp167Glu 9-15 5 Mild ? Boekhorst et al19
    p.Asp167Gly ? ? Mild‡ ? Cutler et al74
    p.Asp542Tyr <1 <1 Severe No Akkarapatumwong et al75
    p.Asp542Gly <1 5 Severe No Higuchi et al76; McGinniss et al77
    p.Asp542His <1 ? Severe No Waseem et al55; Bogdanova et al78
    p.Asp542Ala <1 ? Severe No Tagariello et al, unpublished§
    p.Asp1846Tyr <1 ? Severe No Becker et al79
    p.Asp1846Asn <1 ? Severe No Becker et al79
    p.Asp1846Gly <1 ? Severe No Casana et al80
    p.Asp1846Glu <1 ? Severe No Ljung et al, unpublished§
p.Asn235Ser
    p.Asn235Ile <1 ? Severe ? Bicocchi et al81
    p.Asn235Asp <1 ? Severe No Ljung et al, unpublished§
p.Asn618Ile
    p.Asn618Asp ? ? Severe ? Leuer et al53
    p.Asn618Asp ? ? Moderate ? Arruda et al82
    p.Asn618Ser 31 22 Mild ? Roelse et al45
    p.Asn618Ser 30 ? Mild Yes Vlot et al46
    p.Asn618Ser ? ? Mild ? Boekhorst19
    p.Ans618Ser <1 ? Severe No Ljung et al, unpublished§
    p.Asn1922Asp <1 ? Severe Yes Traystman et al47
    p.Asn1922Asp ? ? Moderate ? Higuchi et al76
    p.Asn1922Ser ? ? Severe ? Higuchi et al76
    p.Asn1922Ser ? ? Moderate ? Diamond et al83
p.Leu242Pro
    p.Leu625Val 8-12 ? Mild No Freson et al49; Gallardo et al, unpublished§
    p.Leu625Ser <1 1 Severe No Guillet et al15
    p.Leu1929Pro ? ? ? ? Cutler et al74
p.Gly261Asp
    p.Gly643Ala* <1 ? Severe No Gallardo et al, unpublished§
    p.Gly1948Asp 7 49 Mild/moderate No David et al18
    p.Gly1948Arg 12 ? Mild No Ljung et al, unpublished§
p.Gly455Val
    p.Ala78Pro <1 ? Severe Yes Sukarova-Stefanovska et al84
    p.Gly455Glu 1 ? Severe Yes Waseem et al55; Vinciguerra et al85
    p.Gly455Arg <1 ? Severe No Freson et al49
p.Gly494Val: p-Gly494Ser 4 23 Moderate Yes Liu et al68
p.Pro550Arg
    p.Ala175Thr 30 ? Mild No Guillet et al15
    p.Pro1854Arg <1 ? Severe No Bogdanova et al78; Becker et al79
    p.Pro1854Leu ? ? Mild ? Lillicrap et al, unpublished§
p.Ala1701Val: p.Ala1701Asp <1 1 Severe No David et al14
p.Phe1743Leu
    p.Phe436Cys 3 ? Moderate No Cutler et al74
    p.Phe436Cys ? ? Mild/moderate ? Bogdanova86
    p.Phe1743Leu 8 ? Mild ? Ahmed et al56
p.Gln2087Pro
    p.Gln2246Arg 4 4 Moderate No Schwaab et al48
    p.Glu2248Arg ? ? Mild/moderate ? Boekhorst et al19
    p.Gln2246Lys 10 4 Mild No David et al14
p.Pro2153Leu
    p.Pro2153Gln 3 6 Moderate No Schwaab et al48
    p.Pro2153Glu 2 <5 Mild/moderate ? Jacquemin et al51
    p.Pro2153Arg <1 <1 Severe No Ivaskevicius et al52; Leuer et al53
    p.Pro2310Leu <1 ? Severe No Bogdanova et al78
p.Ile2317Phe: p.Ser2160Arg 5 ? Moderate ? Ahmed et al56

? indicates not available.

*

Mutation at the topologically equivalent position in human ceruloplasmin A2 domain, p.Gly631Arg, leads to impaired copper incorporation.45

†

Reported as ″severe″ in the HAMSTeRS database.

‡

Reported as ″moderate″ in the HAMSTeRS database. Altogether, absence of a fold-stabilizing side chain and cavity formation at this position appear to have less deleterious effects on the domain structure than clashes between side chains other than Asp and neighboring residues, in particular Trp208 (Figure 3A; Table S1).

§

Unpublished work included in this table has been deposited with the HAMSTeRS database.