Figure 2. Point mutations and inheritance of the SHH, ZIC2, SIX3 and TGIF genes
SHH: 41 different variations (73% missense, 27% nonsense or frameshift mutations); 73% inherited point mutations, predominantly of maternal (67%) rather than paternal (33%) origin. ZIC2: 44 different point mutations (29% missense, 55% nonsense or frameshift, 13% polyalanine tract, 3% splice alterations) with 70% occurring “de novo” and two cases of probable germline mosaicism. SIX3: 18 different point mutations (78% missense, 22% nonsense or frameshift). TGIF: 3 missense mutations and 1 nonsense mutation. The pathogenicity of these alterations has been confirmed by predictive or functional studies.[6, 18, 28, 29, 30] GenBank accession numbers are NM_00193.2 for SHH cDNA, NM_007129.2 for ZIC2 cDNA, NM_005413.2 for SIX3 cDNA and NM_003244.2 for TGIF cDNA.