Table 1

 Pathogenic HNPCC mutations and families negative for the BRAF-V600E mutation

MLH1 germline alterationsMSH2 germline alterations
Number of cases (n = 77)Families (n = 67)Pathogenic alteration*Number of cases (n = 79)Families (n = 78)Pathogenic alteration
*This column shows the type of alterations found in the HNPCC families analysed. Mutations shown as deletions of exon 16 correspond to the 3.5 kb deletion of MLH1 that characterises the commonest Finnish founder mutation. A second MLH1 Finnish founder mutation is also shown in the same column as a G→A 454-1 splice site defect; †These cases were previously analysed21; ‡This mutation introduces a splicing defect in intron 8; §This mutation introduces a splicing defect in intron 5; §Thirty five of these cases were reported previously as BRAF negative.21
Exon deletions (n = 32) Exon deletions (n = 11)
55Deletion exon 622Deletion exon 2
11Deletion exon 1111Deletion exon 8
1916Deletion exon 1611Deletion exon 9
11Deletion exon 1711Deletion exon 12
31Deletion exons 1–1511Deletion exons 1–3
11Deletion exons 1–1611Deletion exons 1–6†
11Deletion exons 4–1111Deletion exons 7–10
11Deletion exons 13–1511Deletion exons 11–14
11Deletion exons 12–16
11Deletion exons 13–15
Missense mutations (n = 20) Missense mutations (n = 1)
21Met (35) Arg11Pro (349) Leu†
52Ser (44) Phe
22Gly (67) Arg
11Ile (68) Asn
77Ile (107) Arg
11Thr (117) Met
11Arg (217) Cys
11Tyr (646) Cys†
Nonsense mutations (n = 5) Nonsense mutations (n = 9)
11Arg (226) Stop†11Gln (298) Stop
32Arg (659) Stop32Arg (406) Stop
11Trp (714) Stop†11Gln (419) Stop
11Leu (458) Stop
11Met (621) Stop
11Gly (759) Stop
11Leu (811) Stop
Nucleotide deletions (n = 5) Nucleotide deletions (n = 7)
1163 Deletion G†1167 Deletion G
11378 Deletion GC11406 Deletion T
11665 Deletion A11811 Deletion TCTG
111852 Deletion AAG†112113 Deletion G†
112179 Deletion CACA†112228 Deletion CATT
112508 Deletion T
112629 Deletion AG
Amino acid deletions (n = 2) Amino acid deletions (n = 1)
22Deletion Lys (616)11Deletion Asn (596)
Nucleotide insertions (n = 3) Nucleotide insertions (n = 2)
11861 Insertion A11679 Insertion A
111490 Insertion C11688 Insertion A
112198 Insertion AAAC†
Splice site mutations (n = 10) Splice site mutations (n = 3)
11IVS8+1 G→T‡22IVS5+3 A→T§
22454−1 G→A111759+2 T→A†
11546−1 G→A†
11790+1 G→A†
11790+1 G→T†
111668−1 G→T†
111989+4 Insertion C†
111989+5 G→C†
112103+1 G→T†
Abnormal IHC (n = 45)§
4545No expression