Preimplantation genetic diagnosis of hemophilia A

Thrombosis Journal

Table 1 Genotype-phenotype relationship, genetic testing and preimplantation genetic diagnosis (PGD) in hemophilia A

Mutation type	Frequency of occurrance^a	Clinical severity^b	Test method	PGD method
Inversion • INV22 • INV1	47 % • 45 % • 2 %	Severe	• I-PCR (for INV22) • Long-distance PCR (for INV22) • Southern blotting (for INV22) • Multiplex PCR (for INV1)	• Linkage analysis
Point mutation • Missense • Nonsense • Splicing site	28 % • 15 % • 10 % • 3 %	Mild, Moderate, Severe • Mild, Moderate (majority) • Severe (majority) • Severe (majority)	Direct DNA sequencing	• ARMS-qPCR • Linkage analysis
Small deletion/insertion (<1 exon)	16 %	Severe (majority)	Direct DNA sequencing	• ARMS-qPCR • Linkage analysis
Large deletion (≥1 exon)	3 %	Severe (majority)	MLPA	• Linkage analysis
Others (e.g., Complex rearrangement)	NA	Severe (majority)	Depending on mutation entities	• Linkage analysis

MLPA multiplex ligation-dependent probe amplification, I-PCR inverse polymerase chain reaction, ARMS amplification refractory mutation system, NA not available
^aSee the review in Gouw et al., [12]
^bHA patients are clinically divided into three different severities based on the residual FVIII coagulant activity (FVIII:C): severe (FVIII:C < 1 % of normal level), moderate (FVIII:C is 1–5 % of normal level) and mild (FVIII:C is 5–30 % of normal level)

ISSN: 1477-9560