Table 2 Cancer predisposition syndromes with high de novo mutation rates
Cancer predisposition syndromeMutation rate per gamete per generation (ref)Proportion of new mutationsProportion of somatic mosaics among sporadic cases (ref)
Familial adenomatous polyposis coli (FAP)9×10−6 (125)10–25%11% (90)
4×10−6 (126)21% (93)
Neurofibromatosis type 1 (NF1)1.4–2.6×10−4 (26)30–50%Unknown
3–5×10−5 (27)
Neurofibromatosis type 2 (NF2)6.5×10−6 (96)49%30–33% (87, 88, 91)
Tuberous sclerosis complex (TSC)2.5×10−5 (127)>50%∼10%* (84)
1.05×10−5 (128)
6×10−6 (129)
Retinoblastoma (RB)1.23×10−5 (130)∼60%6–10%† (83, 135)
6–7×10−6 (131)
9.3–10.9×10−6 (132)
von Hippel–Lindau (VHL)1.4×10−6 (133)Unknown∼5%‡ (86)
4.4×10−6 (134)
  • *Mosaicism was identified in 6/62 unrelated families with mutations in either TSC1 or TSC2.

  • †In 15/156 families with retinoblastoma, mosaicism was identified by Sippel et al83 and in 1/76 patients with unilateral retinoblastoma.135

  • ‡In 2/42 families, parents were mosaic for VHL.