Table 3.

Characteristics of all 164 enrolled siblings in 78 unrelated MIBS families with severe hemophilia A

Family no.
Type of hemophilia A
Type of inhibitor*
Peak titer, BU/mL*
Factor VIII gene mutation
Novel mutation
IL1 beta genotype*
IL4 genotype*
IL10G 134 microsatellite*
1   Severe   High/Low   3000/4   intron 22 inv   No†  A1A1/A1A2   CC/CC   134/NA  
2   Severe   No/No   NA   Ser170X   No   A2A2/A1A2   CC/TT   NA/134  
3   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A1   TT/CC   None with 134  
4   Severe   High/Low   31/2   intron 22 inv   No   A2A2/A1A2   CC/CC   134/NA  
5   Severe   High/No   565/NA   intron 22 inv   No   A2A2/A1A2   CT/CC   134/NA  
6   Severe   No/High   NA/7   delA(3146-3149)   Yes   A1A1/A2A2   CT/CC   134/134  
7   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A2   CC/CT   None with 134  
8   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A2   CC/CC   None with 134  
9   Severe   No/No   NA   IVS6 + 3A > G   No   A1A1/A1A2   CC/CC   None with 134  
10   Severe   No/High   NA/150   Arg427X   No   A1A2/A1A2   TT/CT   None with 134  
11   Severe   High/High   20/566   delAAGA3091-94   No†  A1A1/A1A1   CC/CC   134/134  
12   Severe   Low/No   3/NA   intron 22 inv   No   A1A2/A1A2   TT/TT   None with 134  
13   Severe   High/High   282/6   delT5574   No   A1A1/A1A1   CC/CT   134/134  
14   Severe   No/High   NA/40   delA(3629-3637)   No   A2A2/A2A2   CC/CT   None with 134  
15   Severe   Low/No   4/NA   insA(3864-3870)   No   A1A1/A1A1   CC/CC   134/NA  
16   Severe   High/No   6/NA   Ser535Thr   Yes   A1A1/A1A2   CC/CC   134/NA  
17   Severe   High/High/High   1100/1560/164   intron 22 inv   No   A1A1/A1A1/A1A1   CT/CT/CT   NA/NA/134  
18   Severe   High/No   55/NA   intron 22 inv   No   A1A2/A1A2   TT/CC   None with 134  
19   Severe   No/No   NA   intron 22 inv   No   A2A2/A2A2   CT/CC   None with 134  
20   Severe   High/High   38/300   intron 22 inv   No   A1A2/A2A2   CT/TT   None with 134  
21   Severe   High/Low   153/1   intron 22 inv   No   A1A2/A1A2   CC/CT   None with 134  
22   Severe   No/No   NA   insA(3864-3870)   No   A1A2/A1A2   CC/CC   NA/134  
23   Severe   No/No   NA   Arg2163Leu   Yes   A1A2/A1A2   CC/CC   None with 134  
24   Severe   No/No   NA   Leu1856Arg   Yes   A1A1/A1A1   TT/CT   None with 134  
25   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A2   CC/CC   None with 134  
26   Severe   No/High   NA/1024   intron 22 inv   No   A2A2/A2A2   CT/CC   None with 134  
27   Severe   No/High   NA/22   intron 22 inv   No   A1A1/A1A1   CT/CC   None with 134  
28   Severe   High/High   15/8   intron 22 inv   No   A1A2/A1A2   CC/CC   134/134  
29   Severe   No/High   NA/90   intron 22 inv   No   A1A2/A1A2   CC/CC   None with 134  
30   Severe   Low/High/No   1/70/NA   delT4159   Yes   A1A1/A2A2/A1A2   CC/CT/CC   134/NA/NA  
31   Severe   No/High   NA/26   intron 22 inv   No   A2A2/A2A2   CC/TT   None with 134  
32   Severe   High/No   560/NA   intron 1 inv   No†  A2A2/A1A1   CT/CT   134/134  
33   Severe   No/No   NA   No mutation found   NA   A1A2/A1A1   CT/CT   134/NA  
34   Severe   Low/No   3/NA   intron 22 inv   No   A1A1/A1A2   CC/CC   None with 134  
35   Severe   No/No/No   NA   intron 22 inv   No   A1A1/A2A2/A1A1   All 3 sibs TT   None with 134  
36   Severe   No/High   NA/43   intron 22 inv   No   A1A1/A1A2   CT/CT   None with 134  
37   Severe   No/High/No   NA/146/NA   intron 22 inv   No   A1A1/A1A1/A1A1   CT/CT/CC   None with 134  
38   Severe   Low/No   1/NA   intron 22 inv   No   A1A1/A1A1   CC/CC   None with 134  
39   Severe   High/High   17/150   intron 22 inv   No   A2A2/A1A1   CC/CC   None with 134  
40   Severe   High/High   11/12   intron 22 inv   No   A1A1/A1A2   CC/CC   134/NA  
41   Severe   Low/High   1/6   Trp585Cys   No   A1A2/A1A1   CC/TT   134/NA  
42   Severe   No/No   NA   No mutation found   NA   A2A2/A1A2   CC/CT   NA/134  
43   Severe   Low/No   3/NA   intron 22 inv   No   A1A1/A1A1   CC/CT   None with 134  
44   Severe   No/No   NA   intron 22 inv   No   A1A1/A1A1   CT/CT   None with 134  
45   Severe   High/No   71/NA   Tyr629X   Yes   A1A1/A1A1   CC/CC   134/NA  
46   Severe   High/Low   700/2   intron 22 inv   No   A1A2/A1A2   CC/CC   134/NA  
47   Severe   No/No   NA   intron 22 inv   No   A1A1/A1A1   CT/CT   None with 134  
48   Severe   High/High   840/72   del exon 1-6   No†   A1A2/A2A2   CC/CC   None with 134  
49   Severe   High/High   6/6   intron 1 inv   No   A1A2/A1A2   TT/CT   134/134  
50   Severe   High/High   6/6   intron 22 inv   No   A1A2/A1A2   CT/CT   None with 134  
51   Severe   High/High   6/6   Trp1108X   Yes   A1A1/A1A1   CT/CT   None with 134  
52   Severe   No/High   NA/11   intron 22 inv   No   A1A1/A1A1   CC/CC   None with 134  
53   Severe   No/No   NA   insAC6321   No   A1A1/A1A1   CC/CC   None with 134  
54   Severe   High/No   164/NA   intron 22 inv   No   A1A1/A1A2   CC/TT   134/134  
55   Severe   No/High   NA/14   insA(5955-5961)   No†   A1A2/A1A2   CC/TT   None with 134  
56   Severe   No/High   NA/19   intron 22 inv   No   A1A1/A1A1   CT/CC   NA/134  
57   Severe   High/No   753/NA   intron 22 inv   No   A1A1/A1A1   CT/TT   134/NA  
58   Severe   No/High   NA/68   insA(2940-2945)   No   A2A2/A2A2   CC/CT   None with 134  
59   Severe   No/High   NA/10   delAT1631-1632   Yes   A1A2/A1A2   CC/CC   NA/134  
60   Severe   High/High   6/6   Trp382X   Yes   A1A1/A1A1   CT/CC   134/NA  
61   Moderate   No/No   NA   His209Arg   No   A1A1/A1A1   TT/TT   None with 134  
62   Moderate   No/No   NA   Arg531Cys   No   A1A2/A1A2   CC/CC   None with 134  
63   Moderate   Low/No   3/NA   His209Arg   No   A1A1/A1A1   CC/CC   NA/134  
64   Moderate   No/No   NA   Arg1781Cys   No   A1A1/A1A1   CT/TT   None with 134  
65   Moderate   No/No/No   NA   Arg2163His   No†  A1A1/A1A1/A1A2   CC/CC/CC   None with 134  
66   Moderate   No/High   NA/19   Gly691Trp   No   A1A1/A1A2   CC/CC   None with 134  
67   Moderate   No/No   NA   insA(3629-3637)   No   A2A2/A1A2   CC/CT   NA/134  
68   Moderate   No/High   NA/9   Asp569Glu   Yes   A1A2/A1A2   CC/CC   NA/134  
69   Moderate   Low/Low/Low   2/3/3   Leu184Pro   Yes   A1A1/A1A2/A1A1   CC/CC/TT   134/NA/NA  
70   Moderate   No/No   NA   Val1733Leu   Yes   A2A2/A2A2   CT/CC   NA/134  
71   Moderate   No/Low   NA/1   Pro1761Gln   Yes   A1A1/A1A2   CC/CC   NA/134  
72   Moderate   No/No   NA   Val483Gly   Yes   A1A1/A1A2   CC/CC   None with 134  
73   Mild   No/No/High/No   NA/NA/6/NA   Tyr2105Cys   No†  A1A1/A1A1/A1A1/A1A1   CC/CC/CC/CC   134/NA/134/NA  
74   Mild   Low/Low   2/1   Phe2101Cys   No   A2A2/A2A2   CC/CC   134/134  
75   Mild   High/No   7/NA   Pro1854Leu   No   A2A2/A1A1   CC/CT   NA/134  
76   Mild   No/No   NA   Arg1696Gly   No   A1A1/A1A1   CC/CC   None with 134  
77   Mild   Low/High   1/42   Arg593Cys   No†  A1A1/A1A1   TT/CT   None with 134  
78
 		 Mild
 		 Low/No
 		 2/NA
 		 Arg593Cys
 		 No†
 		 A1A1/A1A2
 		 CT/CC
 		 None with 134
 
Family no.
Type of hemophilia A
Type of inhibitor*
Peak titer, BU/mL*
Factor VIII gene mutation
Novel mutation
IL1 beta genotype*
IL4 genotype*
IL10G 134 microsatellite*
1   Severe   High/Low   3000/4   intron 22 inv   No†  A1A1/A1A2   CC/CC   134/NA  
2   Severe   No/No   NA   Ser170X   No   A2A2/A1A2   CC/TT   NA/134  
3   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A1   TT/CC   None with 134  
4   Severe   High/Low   31/2   intron 22 inv   No   A2A2/A1A2   CC/CC   134/NA  
5   Severe   High/No   565/NA   intron 22 inv   No   A2A2/A1A2   CT/CC   134/NA  
6   Severe   No/High   NA/7   delA(3146-3149)   Yes   A1A1/A2A2   CT/CC   134/134  
7   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A2   CC/CT   None with 134  
8   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A2   CC/CC   None with 134  
9   Severe   No/No   NA   IVS6 + 3A > G   No   A1A1/A1A2   CC/CC   None with 134  
10   Severe   No/High   NA/150   Arg427X   No   A1A2/A1A2   TT/CT   None with 134  
11   Severe   High/High   20/566   delAAGA3091-94   No†  A1A1/A1A1   CC/CC   134/134  
12   Severe   Low/No   3/NA   intron 22 inv   No   A1A2/A1A2   TT/TT   None with 134  
13   Severe   High/High   282/6   delT5574   No   A1A1/A1A1   CC/CT   134/134  
14   Severe   No/High   NA/40   delA(3629-3637)   No   A2A2/A2A2   CC/CT   None with 134  
15   Severe   Low/No   4/NA   insA(3864-3870)   No   A1A1/A1A1   CC/CC   134/NA  
16   Severe   High/No   6/NA   Ser535Thr   Yes   A1A1/A1A2   CC/CC   134/NA  
17   Severe   High/High/High   1100/1560/164   intron 22 inv   No   A1A1/A1A1/A1A1   CT/CT/CT   NA/NA/134  
18   Severe   High/No   55/NA   intron 22 inv   No   A1A2/A1A2   TT/CC   None with 134  
19   Severe   No/No   NA   intron 22 inv   No   A2A2/A2A2   CT/CC   None with 134  
20   Severe   High/High   38/300   intron 22 inv   No   A1A2/A2A2   CT/TT   None with 134  
21   Severe   High/Low   153/1   intron 22 inv   No   A1A2/A1A2   CC/CT   None with 134  
22   Severe   No/No   NA   insA(3864-3870)   No   A1A2/A1A2   CC/CC   NA/134  
23   Severe   No/No   NA   Arg2163Leu   Yes   A1A2/A1A2   CC/CC   None with 134  
24   Severe   No/No   NA   Leu1856Arg   Yes   A1A1/A1A1   TT/CT   None with 134  
25   Severe   No/No   NA   intron 22 inv   No   A1A2/A1A2   CC/CC   None with 134  
26   Severe   No/High   NA/1024   intron 22 inv   No   A2A2/A2A2   CT/CC   None with 134  
27   Severe   No/High   NA/22   intron 22 inv   No   A1A1/A1A1   CT/CC   None with 134  
28   Severe   High/High   15/8   intron 22 inv   No   A1A2/A1A2   CC/CC   134/134  
29   Severe   No/High   NA/90   intron 22 inv   No   A1A2/A1A2   CC/CC   None with 134  
30   Severe   Low/High/No   1/70/NA   delT4159   Yes   A1A1/A2A2/A1A2   CC/CT/CC   134/NA/NA  
31   Severe   No/High   NA/26   intron 22 inv   No   A2A2/A2A2   CC/TT   None with 134  
32   Severe   High/No   560/NA   intron 1 inv   No†  A2A2/A1A1   CT/CT   134/134  
33   Severe   No/No   NA   No mutation found   NA   A1A2/A1A1   CT/CT   134/NA  
34   Severe   Low/No   3/NA   intron 22 inv   No   A1A1/A1A2   CC/CC   None with 134  
35   Severe   No/No/No   NA   intron 22 inv   No   A1A1/A2A2/A1A1   All 3 sibs TT   None with 134  
36   Severe   No/High   NA/43   intron 22 inv   No   A1A1/A1A2   CT/CT   None with 134  
37   Severe   No/High/No   NA/146/NA   intron 22 inv   No   A1A1/A1A1/A1A1   CT/CT/CC   None with 134  
38   Severe   Low/No   1/NA   intron 22 inv   No   A1A1/A1A1   CC/CC   None with 134  
39   Severe   High/High   17/150   intron 22 inv   No   A2A2/A1A1   CC/CC   None with 134  
40   Severe   High/High   11/12   intron 22 inv   No   A1A1/A1A2   CC/CC   134/NA  
41   Severe   Low/High   1/6   Trp585Cys   No   A1A2/A1A1   CC/TT   134/NA  
42   Severe   No/No   NA   No mutation found   NA   A2A2/A1A2   CC/CT   NA/134  
43   Severe   Low/No   3/NA   intron 22 inv   No   A1A1/A1A1   CC/CT   None with 134  
44   Severe   No/No   NA   intron 22 inv   No   A1A1/A1A1   CT/CT   None with 134  
45   Severe   High/No   71/NA   Tyr629X   Yes   A1A1/A1A1   CC/CC   134/NA  
46   Severe   High/Low   700/2   intron 22 inv   No   A1A2/A1A2   CC/CC   134/NA  
47   Severe   No/No   NA   intron 22 inv   No   A1A1/A1A1   CT/CT   None with 134  
48   Severe   High/High   840/72   del exon 1-6   No†   A1A2/A2A2   CC/CC   None with 134  
49   Severe   High/High   6/6   intron 1 inv   No   A1A2/A1A2   TT/CT   134/134  
50   Severe   High/High   6/6   intron 22 inv   No   A1A2/A1A2   CT/CT   None with 134  
51   Severe   High/High   6/6   Trp1108X   Yes   A1A1/A1A1   CT/CT   None with 134  
52   Severe   No/High   NA/11   intron 22 inv   No   A1A1/A1A1   CC/CC   None with 134  
53   Severe   No/No   NA   insAC6321   No   A1A1/A1A1   CC/CC   None with 134  
54   Severe   High/No   164/NA   intron 22 inv   No   A1A1/A1A2   CC/TT   134/134  
55   Severe   No/High   NA/14   insA(5955-5961)   No†   A1A2/A1A2   CC/TT   None with 134  
56   Severe   No/High   NA/19   intron 22 inv   No   A1A1/A1A1   CT/CC   NA/134  
57   Severe   High/No   753/NA   intron 22 inv   No   A1A1/A1A1   CT/TT   134/NA  
58   Severe   No/High   NA/68   insA(2940-2945)   No   A2A2/A2A2   CC/CT   None with 134  
59   Severe   No/High   NA/10   delAT1631-1632   Yes   A1A2/A1A2   CC/CC   NA/134  
60   Severe   High/High   6/6   Trp382X   Yes   A1A1/A1A1   CT/CC   134/NA  
61   Moderate   No/No   NA   His209Arg   No   A1A1/A1A1   TT/TT   None with 134  
62   Moderate   No/No   NA   Arg531Cys   No   A1A2/A1A2   CC/CC   None with 134  
63   Moderate   Low/No   3/NA   His209Arg   No   A1A1/A1A1   CC/CC   NA/134  
64   Moderate   No/No   NA   Arg1781Cys   No   A1A1/A1A1   CT/TT   None with 134  
65   Moderate   No/No/No   NA   Arg2163His   No†  A1A1/A1A1/A1A2   CC/CC/CC   None with 134  
66   Moderate   No/High   NA/19   Gly691Trp   No   A1A1/A1A2   CC/CC   None with 134  
67   Moderate   No/No   NA   insA(3629-3637)   No   A2A2/A1A2   CC/CT   NA/134  
68   Moderate   No/High   NA/9   Asp569Glu   Yes   A1A2/A1A2   CC/CC   NA/134  
69   Moderate   Low/Low/Low   2/3/3   Leu184Pro   Yes   A1A1/A1A2/A1A1   CC/CC/TT   134/NA/NA  
70   Moderate   No/No   NA   Val1733Leu   Yes   A2A2/A2A2   CT/CC   NA/134  
71   Moderate   No/Low   NA/1   Pro1761Gln   Yes   A1A1/A1A2   CC/CC   NA/134  
72   Moderate   No/No   NA   Val483Gly   Yes   A1A1/A1A2   CC/CC   None with 134  
73   Mild   No/No/High/No   NA/NA/6/NA   Tyr2105Cys   No†  A1A1/A1A1/A1A1/A1A1   CC/CC/CC/CC   134/NA/134/NA  
74   Mild   Low/Low   2/1   Phe2101Cys   No   A2A2/A2A2   CC/CC   134/134  
75   Mild   High/No   7/NA   Pro1854Leu   No   A2A2/A1A1   CC/CT   NA/134  
76   Mild   No/No   NA   Arg1696Gly   No   A1A1/A1A1   CC/CC   None with 134  
77   Mild   Low/High   1/42   Arg593Cys   No†  A1A1/A1A1   TT/CT   None with 134  
78
 		 Mild
 		 Low/No
 		 2/NA
 		 Arg593Cys
 		 No†
 		 A1A1/A1A2
 		 CT/CC
 		 None with 134
 

Numbering of the mutations was according to cDNA. Siblings are numbered in consecutive order, with sibling 1 the oldest brother.

*

All values are for siblings 1/2/3/4.

†

Mutation previously associated with inhibitors.

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