Table 1 Patient characteristics, mutations and functional data
Patient*HPE typeDNA alteration (location) in SIX3Predicted protein alteration in SIX3Functional studies†47GenderProband/ relativeRef.
1Not specifiedc.109G→T (NTD)p.G37C0.5–0.9FemaleProbandNA
2‡Lobarc.109G→T (NTD)p.G37C0.5–0.9MaleProband42
3a‡MIHVc.109G→T (NTD)p.G37C0.5–0.9FemaleProbandNA
3b‡Nonec.109G→T (NTD)p.G37C0.5–0.9FemaleMotherNA
4a‡Alobarc.206G→A (NTD)c.G69D>0.9FemaleProband48
c.406dupGC (SD)FS<0.5
4b‡Nonec.206G→A (NTD)c.G69D>0.9MaleFather4848
c.406dupGC (SD)FS<0.5
4cNonec.206G→A (NTD)c.G69D>0.9FemalePaternal grandmother48
c.406dupGC (SD)FS<0.5Female48
5a‡Alobarc. 214G→C (NTD)p.A72P<0.5FemaleProband48
5b‡Nonec. 214G→C (NTD)p.A72P<0.5FemaleMother48
6Alobarc.235A→G (NTD)p.M79VUnknownNot specifiedProband47
7a‡AlobarNot specified (SD)p.V92G<0.5MaleProband45
7b‡AlobarNot specified (SD)p.V92G<0.5MaleBrother45
7c‡AlobarNot specified (SD)p.V92G<0.5MaleBrother45
7d‡MicroformNot specified (SD)p.V92G<0.5FemaleMother45
8‡Semilobarc.275T→G (SD)p.V92G<0.5FemaleProband43
9‡Semilobarc.278C→A (SD) (PTCH1: c.1165G→A)p.A93D (PTCH1: p.A393T)<0.5FemaleProband22 42
10a‡Alobarc.311A→G (SD)p.D104G0.5–0.9MaleProband48
10b‡Nonec.311A→G (SD)p.D104G0.5–0.9MaleFather48
11‡Not specifiedc.313A→G (SD)p.I105V>0.9Not specifiedProband43
12‡Lobarc.338G→A (SD)p.W113X<0.5MaleProband42
13a‡Not specifiedc.339G→A (SD)p.W113X<0.5MaleProbandNA
13b‡Not specifiedNot testedNot testedNot testedMaleBrotherNA
13c‡Microformc.339G→A (SD)p.W113X<0.5FemaleMotherNA
14a‡Alobarc.339G→T (SD)p.W113C<0.5FemaleProband42
14b‡Microformc.339G→T (SD)p.W113C<0.5FemaleMother42
14c‡Microformc.339G→T (SD)p.W113C<0.5FemaleMaternal aunt42
14d‡Microformc.339G→T (SD)p.W113C<0.5MaleMaternal uncle42
14e‡Nonec.339G→T (SD)p.W113C<0.5FemaleMaternal aunt42
14f‡Microformc.339G→T (SD)p.W113C<0.5FemaleMaternal grandmother42
14g‡MicroformLinkage onlyLinkage onlyLinkage onlyMaleMaternal great uncle42
14h‡NoneLinkage onlyLinkage onlyLinkage onlyFemaleMaternal first cousin42
14i‡Not specifiedLinkage onlyLinkage onlyLinkage onlyFemaleMaternal half-sister42
14jNot specifiedNot testedNot testedNot testedFemaleMaternal first cousin42
14k‡Not specifiedNot testedNot testedNot testedMaleMaternal first cousin42
14l‡Not specifiedNot testedNot testedNot testedFemaleMaternal first cousin42
14mNot specifiedNot testedNot testedNot testedFemaleMaternal first cousin, once removed42
14nNot specifiedNot testedNot testedNot testedMaleMaternal great uncle42
14oNot specifiedNot testedNot testedNot testedNot specifiedMaternal great-grandparent42
15‡Semilobarc.341C→T (SD)p.S114L<0.5FemaleProband42
16a‡Lobarc.385G→T (SD)p.E129X<0.5MaleProband42
16b‡Alobarc.385G→T (SD)p.E129X<0.5FemaleSister42
16c‡Microformc.385G→T (SD)p.E129X<0.5MaleFather42
17Not specifiedc.389C→A (SD)p.S130X<0.5MaleProband42
18a‡Alobarc.404G→C (SD)p.R135P<0.5MaleProband48
18b‡Nonec.404G→C (SD)p.R135P<0.5FemaleMother48
19Not specifiedc.404_407dupGCGC (SD)FS<0.5FemaleProband42
20‡Semilobarc.405_409CGCCG (SD)FS<0.5MaleProband42
21aNot specifiedc.463_465delCAC (SD)p.H155delUnknownNot specifiedProband47
21bNot specifiedc.463_465delCAC (SD)p.H155delUnknownFemaleMother47
22‡Not specifiedc.469T→A (SD)p.F157I<0.5MaleProband42
23a‡Alobarc.507delG (SD)FS<0.5FemaleProband48
23b‡Nonec.507delG (SD)FS<0.5MaleFather48
24a‡Lobarc.515C→T (SD)p.A172V0.5–0.9MaleProband42
24b‡SemilobarNot testedNot testedNot testedFemaleSister42
24c‡Not specifiedNot testedNot testedNot testedFemaleMother42
25aAlobarc.518A→C (SD)p.H173P0.5–0.9FemaleProband45
25bNonec.518A→C (SD)p.H173P0.5–0.9FemaleMother45
26aSemilobarc.518A→C (SD)p.H173P0.5–0.9FemaleProband43
26bNonec.518A→C (SD)p.H173P0.5–0.9FemaleMother43
26cNonec.518A→C (SD)p.H173P0.5–0.9FemaleMaternal aunt43
26dNot specifiedNot testedNot testedNot testedNot specifiedMaternal first cousin43
26eNot specifiedNot testedNot testedNot testedNot specifiedMaternal first cousin43
26fNot specifiedNot testedNot testedNot testedNot specifiedMaternal first cousin43
27‡Not specifiedc.520T→C (SD)p.Y174H0.5–0.9FemaleProband42
28a‡Alobarc.542_576dup (SD)FSUnknownFemaleProband43 45
28b‡Nonec.542_576dup (SD)FSUnknownMaleFather43 45
29‡Semilobarc.551delC (SD)FS<0.5FemaleProband42
30a‡Alobarc.556_557dupGG (SD)FS<0.5FemaleProband44 45
30b‡Alobarc.556_557dupGG (SD)FS<0.5MaleBrother44 45
30c‡Alobarc.556_557dupGG (SD)FS<0.5FemaleSister44 45
30d‡Not specifiedc.556_557dupGG (SD)FS<0.5FemaleSister44 45
30e‡Microformc.556_557dupGG (SD)FS<0.5MaleFather44 45
31a‡AlobarNot testedNot testedNot testedFemaleProband42
31b‡Semilobarc.582dup C (SD)FS<0.5FemaleSister42
31c‡Microformc.582dup C (SD)FS<0.5MaleFather42
32a‡Semilobarc.605C→T (SD)p.T202I<0.5FemaleProband43 45
32b‡Nonec.605C→T (SD)p.T202I<0.5FemaleMother43 45
33a‡Semilobarc.619G→T (HD)p.E207X<0.5MaleProband42
33b‡Alobarc.619G→T (HD)p.E207X<0.5FemaleSister42
34Not specifiedc.637T→G (HD)p.F213V<0.5MaleProband42
35‡Lobarc.652C→T (HD)p.R218W0.5–0.9FemaleProband42
36‡Not specifiedc. 653G→C (HD)p.R218P<0.5FemaleProband42
37‡Not specifiedc.676C→G (HD)p.L226V>0.9FemaleProband19 52
38Not specifiedc.680A→C (HD)p.Q227P0.5–0.9Not specifiedProband42
39‡Microformc.686C→T (HD)p.P229LUnknownMaleProband46
40‡Alobarc.692C→G (HD)p.P231R<0.5FemaleProband45
41‡Alobarc.698_706del (HD)p.N233_S235del<0.5FemaleProband19 39
42Not specifiedc.GC718_719AA (HD)p.A240K<0.5Not specifiedProband42
43a‡Not specifiedc.721C→T (HD)p.Q241XUnknownMaleProband42
43bNot specifiedNot testedNot testedUnknownNot specifiedSibling42
43c‡Nonec.721C→T (HD)p.Q241XUnknownFemaleMother42
44Not specifiedc.730G→T (HD)p.G244C<0.5Not specifiedProband42
45Not specifiedc.736delA (HD)FSUnknownNot specifiedProband47
46Not specifiedc.743_745delCAG (HD) (TGIF: c.478C→T)p.248K delQ (TGIF: p.160S)UnknownFemaleProbandNA
47a‡Microformc.749T→C (HD)p.V250A0.5–0.9MaleProband19
47b‡Nonec.749T→C (HD)p.V250A0.5–0.9FemaleMother19
47c‡Nonec.749T→C (HD)p.V250A0.5–0.9FemaleMaternal aunt19
47d‡Alobarc.749T→C (HD)p.V250A0.5–0.9Not specifiedSibling19
47e‡Alobarc.749T→C (HD)p.V250A0.5–0.9Not specifiedSibling19
47fAlobarc.749T→C (HD)p.V250A0.5–0.9Not specifiedSibling19
48Not specifiedc.762T→A (HD)p.F254L0.5–0.9MaleProband42
49‡Not specifiedc.769C→T (HD)p.R257W<0.5FemaleProband42
50aSemilobarc. 769C→T (HD)p.R257W<0.5FemaleProband43 45
50bAlobarNot testedNot testedNot testedMaleBrother43 45
50c‡Nonec. 769C→T (HD)p.R257W<0.5MaleFather43 45
51aLobarc. 769C→G (HD)p.R257GUnknownNot specifiedProband47
51bNot specifiedc. 769C→G (HD)p.R257GUnknownMaleFather47
52‡Semilobarc.770G→C (HD)p.R257P>0.9FemaleProband19 52
53Not specifiedc.773G→C (HD)p.R258L<0.5Not specifiedProband42
54Not specifiedc.785G→A (HD)p.R262H0.5–0.9Not specifiedProband42
55aNot specifiedNot testedNot testedUnknownNot specifiedProband47
55bNoneNot testedNot testedUnknownNot specifiedObligate carrier47
55cNot specifiedc.806G→C (CTD)p.R269TUnknownMaleGrandfather47
56a‡Semilobarc.806G→T (CTD)p.R269MUnknownFemaleProband47 51
56b‡AlobarNot testedNot testedUnknownMaleSibling47
56c‡Lobarc.806G→T (CTD)p.R269MUnknownMaleSibling47
56d‡Microformc.806G→T (CTD)p.R269MUnknownFemaleMother47 51
57Semilobarc.806+1G→T (CTD)SpliceUnknownNot specifiedProband47
58‡Not specifiedc.G807C (CTD)p.R269S0.5–0.9MaleProband42
59Not specifiedc.820_832delinsCTGGACCT (CTD)p.A274XUnknownMaleProbandNA
60Semilobarc.850G→C (CTD) (ZIC2: c.910T→C)p.A284P (ZIC2: p.W304R)UnknownFemaleProbandNA
61‡Semilobarc.890C→T (CTD)p.P297L0.5–0.9FemaleProband42
62‡Semilobarc.944C→T (CTD)p.T315IUnknownFemaleProband48
63Not specifiedDeletionNAUnknownNot specifiedProband47
64Not specifiedMicrodeletion by qPCRNAUnknownNot specifiedProband40 41
65Not specifiedMicrodeletion by qPCRNAUnknownNot specifiedProband40 41
66Not specifiedMicrodeletion by qPCRNAUnknownNot specifiedProband41
67Not specifiedMicrodeletion by qPCRNAUnknownFemaleProband41
68‡Semilobardel(2)(p2101p2109)NAUnknownFemaleProband38 49
69‡Nonedel(2)(p21)NAUnknownMaleProband38
70‡Semilobardel(2)(p21p23)NAUnknownMaleProband38
71‡Semilobardel(2)(p16p22)NAUnknownFemaleProband38
72Lobardel(2)(p21p22.2)NAUnknownFemaleProband38 50
73‡Alobardel(2)(p21p22.1)NAUnknownMaleProband38
74‡Semilobarinv ins(2)(p21q24q13)NAUnknownFemaleProband38
75‡Semilobart(1;2)(p21;p21)NAUnknownMaleProband38
76Alobart(1;2)(p22.3;p21)NAUnknownMaleProband38
77‡Lobardel(2)(p16.3p21)§NAUnknownMaleProbandNA

  • CTD, C-terminal domain; HD, homeodomain; HPE, holoprosencephaly; MIHV, middle interhemispheric variant; NA, not applicable (unpublished when seeming in the Reference column); NTD, N-terminal domain; qPCR, quantitative PCR: SD, SIX domain.

  • *Each kindred is numbered separately; within a kindred, individual members have separate letter identifier.

  • †Protein Activity Index.

  • ‡Clinical information available.

  • §Complex rearrangement additionally resulting in chromosome 2 inversion, translocation involving chromosomes 7, 13 and 18 and deletions of regions of chromosomes 7 and 18.