Table 3 Estimates of the proportion of different mutation types and mutation‐negative de novo cases and potential offspring risks.
| Sporadic case bilateral VS at presentation (proportion of unfound mutations in blood) | Sporadic case unilateral VS at presentation (proportion of unfound mutations in blood) | |
|---|---|---|
| Point mutation in blood non‐mosaic (actual) | 94/217 (43) | 28/103 (27) |
| MLPA mutation in blood (actual) | 24/217 (11) | 1/103 (1) |
| Point mutation detected in blood mosaic (actual) | 19/217 (9) | 5/103 (5) |
| (A) Point mutation detectable from tumour (estimate) | 43/217 (20) | 46/103 (45) |
| [43/80–54%] | [46/69–67%] | |
| (B) Undetectable mutation in blood (estimate) | 11/217 (5) | 3/103 (3) |
| [11/80–14%] | [3/69–4%] | |
| (C) MLPA detectable abnormality in mosaic form (estimate) | 19/217 (9) | 14/103 (14) |
| [19/80–24%] | [14/69–20%] | |
| (D) Undetectable mosaic mutation (estimate) | 6/217 (3) | 6/103 (6) |
| [7/80–9%] | [6/69–9%] | |
| (E) Offspring risk if mutation negative in blood | 2.7%+7%+2.3%+0.9% | 3.3%+2%+2%+1% |
| 13% (1 in 8) | 8.3% (1 in 12) |
MLPA, multiple ligation‐dependent probe amplification; VS, vestibular schwannoma.
(A) The proportion of point mutations that would be detectable if tumour material were available from all patients.
(B) Mutations that are present in full form but refractory to current mutation detection techniques (9% in multigenerational families). The assumption is that an additional 9–10% of detectable mutations in blood would be undetectable. For UVS 29+1/103 detectable in full form, assume 3 undetectable.
(C) Estimate of the number of MLPA‐detectable abnormalities present in mosaic form. Assumptions are that 20–25% of missed mutations will be MLPA‐detectable mosaic mutations.
(D) The number of mosaic mutations that would not be detected using current techniques. Again, the assumption is that 9% of non‐detectable mosaic mutations will be in this category.
(E) The offspring risk is calculated from the following. The risk from row (A) is minimal, as shown from 0/34 children (95% CI for 0/34: 0% to 8.4%—assume 5%); (B) 50% offspring risk if present in all cells; (C/D) assume 10% (7/70 children of proven mosaics have developed NF2) as the proportion of mutations in blood is not estimable.