Mild Hemophilia A With Arg593 to Cys (Seattle Series)
| Family/Patient . | Factor VIII Level (%) . | Haplotype* . | Comments . | |||||
|---|---|---|---|---|---|---|---|---|
| . | VIII:C . | VIII:Ag . | Bcl I . | Xba I . | Int 7 . | Int 13 . | Int 22 . | . |
| A | 10 | 45 | − | + | d | b | Previously reported17 | |
| B1 | 10 | 50 | − | − | − | b | b | |
| B2 | 12 | 53 | − | − | Brother of B1 | |||
| B3 | 24 | 48 | Cousin of B1 | |||||
| B4-8 | 10-19 | − | 5 affected uncles & cousins | |||||
| C | 12 | 57 | − | − | − | b′ | e | Post DDAVP VIII:C to 50% |
| D1 | 8 | 47 | + | + | c | d | De novo, mutation† | |
| D2 | 9 | 56 | + | Nephew of D1 | ||||
| E | 14 | 44 | + | + | c | c | Factor VR/Q506 | |
| F | 8, 10, 11 | 79‡ | + | + | c | c | Patient with inhibitor | |
| Family/Patient . | Factor VIII Level (%) . | Haplotype* . | Comments . | |||||
|---|---|---|---|---|---|---|---|---|
| . | VIII:C . | VIII:Ag . | Bcl I . | Xba I . | Int 7 . | Int 13 . | Int 22 . | . |
| A | 10 | 45 | − | + | d | b | Previously reported17 | |
| B1 | 10 | 50 | − | − | − | b | b | |
| B2 | 12 | 53 | − | − | Brother of B1 | |||
| B3 | 24 | 48 | Cousin of B1 | |||||
| B4-8 | 10-19 | − | 5 affected uncles & cousins | |||||
| C | 12 | 57 | − | − | − | b′ | e | Post DDAVP VIII:C to 50% |
| D1 | 8 | 47 | + | + | c | d | De novo, mutation† | |
| D2 | 9 | 56 | + | Nephew of D1 | ||||
| E | 14 | 44 | + | + | c | c | Factor VR/Q506 | |
| F | 8, 10, 11 | 79‡ | + | + | c | c | Patient with inhibitor | |
Abbreviations: VIII:C, factor VIII clotting activity, VIII:Ag, antigen level (see Materials and Methods).
Bcl I (intron 18), Xba I (intron 22), and AlwNI-detected (intron 7) dimorphisms are + for present and − for absent restriction sites. Intron (Int) 13 and 22 CA repeats are summarized as most frequent (common) number (c). For intron 13, b, b′ are 2 and 4 bp smaller than c, respectively, and d is 6 bp larger than c; for intron 22, b is 2 bp smaller, d is 2 bp larger, and e is 4 bp larger than c.
Patient D1's mother (but not his maternal grandmother) is a heterozygous carrier of the Cys593 mutation; the patient's haplotype is that of his unaffected maternal grandfather and differs from both alleles at his maternal grandmother's intron 13 and her intron 22 CA repeat sites.
Antigen level was from a 12-hour postinfusion trough sample drawn after his inhibitor had developed; baseline factor VIII clotting activity is averaged from three samples drawn before his inhibitor was present.