Skip to main content

Advertisement

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

From: Preimplantation genetic diagnosis of hemophilia A

Mutation type Frequency of occurrancea Clinical severityb 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
  1. MLPA multiplex ligation-dependent probe amplification, I-PCR inverse polymerase chain reaction, ARMS amplification refractory mutation system, NA not available
  2. aSee the review in Gouw et al., [12]
  3. 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)