Table 1.
SHH mutations identified in this study. Novel variants are in bold type.
| Subject | cDNA | protein | function | Reference |
|---|---|---|---|---|
| 1 | c.9_12dup | p.Arg6GlyfsX59 | frameshift | Nanni 1999 |
| 2 | c.17G>C | p.Arg6Thr | Signal peptide | Dubourg 2004 |
| 3 | c.38_45del | p.Val13AlafsX48 | frameshift |
Nanni 1999; GeneDx confirmed |
| 4 | c.50T>C | p.Leu17Pro | Signal peptide | Kato 2000 |
| 5 | c.72C>A | p.Cys24X | Palmitoylation site |
Dubourg 2004; NIH new |
| 6 | c.77C>T | p.Pro26Leu |
Palmitoylation site and multimerization |
GeneDx new; see Goetz 2006 |
| 7 | c.80G>C | p.Gly27Ala | Palmitoylation site and multimerization |
Hehr 2004 |
| 8 | c.87delG | p.Gly29fsX11 | frameshift | Rennes new |
| 9 | c.91G>A | p.Gly31Arg | SHH-N | Roessler 1996 |
| 10 | c.116T>C | p.Leu39Pro | SHH-N | GeneDX new |
| 11 | c.108_109delinsG | p.Lys38SerfsX2 | frameshift | NIH new |
| 12 | c.119_120delCC | p.Pro41PhefsX22 | frameshift | Rennes new |
| 13 | c.136C>T | p.Gln46X | truncation | NIH new |
| 14 | c.148_166del | p.Asn50X | truncation | Maastrict new |
| 15 | c.157G>A | p.Glu53Lys | SHH-N | Rennes new |
| 16 | c.210dupC | p.Glu71ArgfsX4 | frameshift | GeneDx new |
| p.Gly290Asp | SHH-C | See 89 | ||
| 17 | c.211delG | p.Glu71SerfsX27 | frameshift | Dubourg 2004 |
| 18 | c.248A>T | p.Asp83Val | SHH-N | Rennes new |
| 19 | c.250A>T | p.Ile84Phe | SHH-N | NIH new |
| 20 | c.263A>T | p.Asp88Val | SHH-N |
Nanni 1999: Heussler 2002; Regensburg new |
| 21 | c.298delC | p.Gln100ArgfsX7 | frameshift | GeneDx new |
| 22 | c.298C>T | p.Gln100X | truncation |
Roessler 1996; Rennes new |
| 23 | c.300G>C | p.Gln100His | SHH-N |
Dubourg 2004; Bertolacini 2009 |
| 24 | c.304T>C | p.Cys102Arg | SHH-N |
Maastricht new |
| 25 | c.305G>A | p.Cys102Tyr | SHH-N | Rennes new |
| 26 | c.316_321del | p.Leu106_Asn107del | deletion | Dubourg 2004 |
| 27 | c.313A>T | p.Lys105X | truncation | Roessler 1996 |
| 28 | c.327G>T | p.Leu109Phe | SHH-N | GeneDx new |
| 29 | c.328G>A | p.Ala110Thr | SHH-N | GeneDx new |
| 30 | c.329C>A | p.Ala110Asp | SHH-N | Dubourg 2004 |
| 31 | c.331A>T | p.Ile111Phe | SHH-N | Nanni 2001 |
| 32 | c.332T>A | p.Ileu111Asn | SHH-N | El-Jaick 2005 |
| 33 | c.345C> A | p.Asn115Lys | SHH-N | Nanni 1999 |
| 34 | c.349T>G | p.Trp117Gly | SHH-N | Roessler 1996 |
| 35 | c.349T>C | p.Trp117Arg | SHH-N | Roessler 1996 |
| 36 | c.355G>T | p.Gly119X | truncation | NIH new |
| 37 | c.370G>A | p.Val124Met | SHH-N | GeneDx new |
| 38 | c.383G>A | p.Trp128X | truncation | Marini 2003 |
| 39 | c.388G>T | p.Glu130X | truncation |
Dubourg 2004; NIH new |
| 40 | c.406G>A | p.Glu136Lys | SHH-N | Bertolacini 2009 |
| 41 | c.415_416del | p.Leu139AlafsX13 | frameshift | NIH new |
| 42 | c.419A>C | p.His140Pro | SHH-N | Orioli 2001 |
| 43 | c.420C>G | p.His140Gln | SHH-N | Ribiero 2005 |
| 44 | c.428G>A | p.Gly143Asp | SHH-N | NIH new |
| 45 | c.431G>C | p.Arg144Pro | SHH-N | GeneDx new |
| 46 | c.439G>A | p.Asp147Asn | SHH-N | GeneDx new |
| 47 | c.449C>G | p.Thr150Arg | SHH-N |
Dubourg 2004; NIH new |
| 48 | c.449C>A | p.Thr150Lys | SHH-N | Rennes new |
| 49 | c.468C>A | p.Ser156Arg | SHH-N | NIH new |
| 50 | c.474C>G | p.Tyr158X | truncation | Dubourg 2004 |
| 51 | c.509T>G | p.Phe170Cys | SHH-N | NIH new |
| 52 | c.511G>C | p.Asp171His | SHH-N | Rennes new |
| 53 | c.525C>G | p.Tyr175X | SHH-N |
Regensburg new |
| 54 | c.526_534del | p.Glu176_Lys178del | deletion | Dubourg 2004 |
| 55 | c.547T>C | p.Cys183Arg | SHH-N | NIH new |
| 56 | c.548G>T | p.Cys183Phe | SHH-N | Orioli 2001 |
| 57 | c.548G>A | p.Cys183Tyr | SHH-N |
Regensburg new |
| 58 | c.551C>T | p.Ser184Leu | SHH-N | NIH new |
| 59 | c.562G>C | p.Glu188Gln | SHH-N | Dubourg 2004 |
| 60 | c.562+1G>A | Splice donor | frameshift | NIH new |
| 61 | c.584_598del | p.196_200del |
Cholesterol addition site |
NIH new; GeneDx confirmed |
| 62 | c.587delG | p.Gly196GlufsX20 |
Cholesterol addition site |
Rennes new |
| 63 | c.587G>A | p.Gly196Glu |
Cholesterol addition site |
Rennes new |
| 64 | c.590G>T | p.Gly197Val |
Cholesterol addition site |
NIH new |
| 65 | c.592T>A | p.Cys198Ser |
Cholesterol addition site |
Rennes new |
| 66 | c.593G>A | p.Cys198Phe | Cholesterol addition site |
Bertolacini 2009 |
| 67 | c.624_625delinsTT | p.Glu208AspfsX1 | frameshift | GeneDx new |
| 68 | c.625C>T | p.Gln209X | truncation | Nanni 1999 |
| 69 | c.653T>C | p.Leu218Pro | SHH-C | Richieri_Costa 2006 |
| 70 | c.664G>A | p.Asp222Asn | SHH-C | Dubourg 2004 |
| 71 | c.671T>A | p.Val224Glu | SHH-C | Roessler 1997 |
| 72 | c.676G>A | p.Ala226Thr | SHH-C | Roessler 1997 |
| 73 | c.692G>T | p.Gly231Val | SHH-C | NIH new |
| 74 | c.694C>G | p.Arg232Gly | SHH-C | GeneDx new |
| 75 | c.701T>C | p.Leu234Pro | SHH-C | GeneDx new |
| 76 | c.707G>A | p.Ser236Asn | SHH-C | Rennes new |
| 77 | c.708C>A | p.Ser236Arg | SHH-C | Nanni 1999 |
| 78 | c.721T>C | p.Phe241Val | SHH-C | Rennes new |
| 79 | c.723C>G | p.Phe241Leu | SHH-C | NIH new |
| 80 | c.764T>A | p.Ile255Asn | SHH-C | NIH new |
| 81 | c.766G>T | p.Glu256X | truncation |
Nanni 1999; GeneDx confirmed |
| 82 | c.787_807del | p.Arg263_Ala269del | deletion | Roessler 1997a |
| 83 | c.800C>T | p.Thr267Ile | SHH-C | Hehr 2004 |
| 84 | c.812T>C | p.Leu271Pro | SHH-C | Dubourg 2004 |
| 85 | c.824C>A | p.Ala275Glu | SHH-C | GeneDx new |
| 86 | c.839C>G | p.Ser280Trp | SHH-C |
Regensburg new |
| 87 | c.839C>A | p.Ser280X | truncation | Richieri-Costa 2006 |
| 88 | c.850G>T | p.Glu284X | truncation | Roessler 1997a; Hehr 2004 |
| 89 | c.869G>A | p.Gly290Asp | SHH-C |
Nanni 1999; Schell-Apacik 2009; GeneDx new; |
| 90 | c.887G>C | p.Gly296Ala | SHH-C | GeneDx new |
| 91 | c.928C>T | p.Arg310Cys | SHH-C | Rennes new |
| 92 | c.961C>A | p.Arg321Ser | SHH-C | NIH new |
| 93 | c.995T>C | p.Val332Ala | SHH-C |
Dubourg 2004; Garavelli 2004 |
| 94 | c.1015G>T | p.Glu339X | truncation | Rennes new |
| 95 | c.1037C>T | p.Ala346Val | SHH-C | NIH new |
| 96 | c.1040C>G | p.Pro347Arg | SHH-C |
NIH new, Rennes new |
| 97 | c.1040C>A | p.Pro347Gln | SHH-C | Dubourg 2004 |
| 98 | c.1040C>T | p.Pro347Leu | SHH-C | Rennes new |
| 99 | c.1051C>T | p.Gln351X | truncation | GeneDx new |
| 100 | c.1061T>C | p.Ile354Thr | SHH-C | Dubourg 2004 |
| 101 | c.1085C>T | p.Ser362Leu | SHH-C | NIH new |
| 102 | c.1088G>A | p.Cys363Tyr | SHH-C | Richieri-Costa 2006 |
| 103 | c.1091A>G | p.Tyr364Cys | SHH-C | Rennes new |
| 104 | c.1117G>A | p.Ala373Thr | SHH-C | NIH new; Hehr 2004 |
| 105 | c.1121A>G | p.His374Arg | SHH-C | NIH new |
| 106 | c.1127C>A | p.Ala376Asp | SHH-C | NIH new |
| 107 | c.1130T>C | p.Phe377Ser | SHH-C |
Regensburg new |
| 108 | c.1132_1140del | p.378_380del | deletion | Nanni 1999 |
| 109 | c.1142G>C | p.Arg381Pro | SHH-C | Dubourg 2004 |
| 110 | c.1145T>C | p.Leu382Pro | SHH-C |
Maastricht new |
| 111 | c.1147G>A | p.Ala383Thr | SHH-C | Roessler 1997a; Hehr 2004 |
| 112 | c.1171G>A | p.Ala391Thr | SHH-C |
Regensburg new |
| 113 | c.1204_1227del | p.402_409del | deletion | Schimmenti 2003 |
| 114 | c.1213_1227del | p.405_409del | deletion | Nanni 1999 |
| 115 | c.1231_1233dup | p.Gly411dup | duplication | NIH new |
| 116 | c.1246A>G | p.Thr416Ala | SHH-C | NIH new |
| 117 | c.1270C>G | p.Pro424Ala | SHH-C | Nanni 1999 |
| 118 | c.1303T>A | p.Tyr435Asn | SHH-C | NIH new |
| 119 | c.1307C>T | p.Ser436Leu | SHH-C | Nanni 1999 |
| 120 | c.1366G>C | p.Gly456Arg | SHH-C | NIH new |
| 121 | c.1370delT | p.Met457ArgfsX18 | frameshift | NIH new |
Descriptions of mutations are based on the NM_000193.2 reference sequence, follow HGVS recommendations (www.hgvs.org/mutnomen) and were checked using the Mutalyzer software for the predicted effects on the reference gene (www.lovd.nl/mutalyzer/1.0.1/). Position +1 refers to the A position of the ATG initiation codon for that gene.