Table 1.
Mutations and clinical details in new cases of pachyonychia congenita
| Family | Mutation – protein change | DNA change | Unreported or known | Familial or spontaneous | Plantar pain | Palmoplantar keratoderma | Thickened nails | Oral leucokeratosis | Cysts and/or follicular hyperkeratosis | Born with teeth? |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | K6a p.Glu163Lys | c.487G>A | Known | Familial | Somewhat painful | PPK | All 20 | Yes | NA | No |
| 2 | K6a p.Leu170Phe | c.508C>T | Known | Spontaneous | Not painful | PPK, very mild | All 20 | No | NA | No |
| 3 | K6a p.Asn172del | c.516_518delCAA | Known | Familial | Very painful, but does not use medication | PK | All 20 | No | NA | No |
| 4 | K6a p.Asn172del | c.516_518delCAA | Known | Familial | Very painful, but does not use medication | PPK | All 20 | Yes | NA | No |
| 5 | K6a p.Asn172del | c.516_518delCAA | Known | Spontaneous | NA; under 2 years old | NA; under 2 years old | 10 fingernails, 2 toenails | Yes | NA | No |
| 6 | K6a p.Asn172del | c.516_518delCAA | Known | Spontaneous | Very painful, but does not use medication | PPK | All 20 | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 7 | K6a p.Asn172del | c.516_518delCAA | Known | Spontaneous | Very painful, but does not use medication | PPK | All 20 | Yes | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 8 | K6a p.Asn172del | c.516_518delCAA | Known | Spontaneous | Somewhat painful | PPK | All 20 | Yes | Steatocystoma, follicular hyperkeratosis | No |
| 9 | K6a p.Asn172del | c.516_518delCAA | Known | Familial | Not painful | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 10 | K6a p.Asn172del | c.516_518delCAA | Known | Spontaneous | Often requires medication to handle the pain | PPK | All 20 | Yes | NA | No |
| 11 | K6a p.Asn172del | c.516_518delCAA | Known | Spontaneous | Somewhat painful | PPK | All 20 | Yes | NA | No |
| 12 | K6a p.Asn172del | c.516_518delCAA | Known | Familial | Often requires medication to handle the pain | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 13 | K6a p.Phe174Ile | c.520T>A | Unreported | Spontaneous | Very painful, but does not use medication | PK | All 20 | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 14 | K6a p.Phe174Ser | c.521T>C | Known | Spontaneous | Very painful, but does not use medication | PK | All 20 | Yes | NA | No |
| 15 | K6a p.Ile178Asn | c.533T>A | Known | Spontaneous | Very painful, but does not use medication | PK | All 20 | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 16 | ND | c.541–1G>C | Known | Familial | Often requires medication to handle the pain | PK | 6 fingernails, 10 toenails | Yes | NA | No |
| 17 | K6a p.Val181_Gln186del | c.541–2A>G | Known | Familial | Somewhat painful | PK | All 20 | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 18 | K6a p.Val181_Gln186del | c.541–2A>G | Known | Familial | Very painful, but does not use medication | PPK | All 20 | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 19 | K6a p.Val181_Gln186del | c.541–2A>G | Known | Familial | Very painful, but does not use medication | PK | All 20 | Yes | NA | No |
| 20 | ND | c.541–2A>C | Known | Spontaneous | Somewhat painful | PK | 5 fingernails, 10 toenails | Yes | NA | No |
| 21 | K6a p.Glu461Ter | c.1381G>T | Unreported | Spontaneous | Very painful, but does not use medication | PK | 5 fingernails, 10 toenails | Yes | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 22 | K6a p.Ile462Asn | c.1385T>A | Known | Spontaneous | Very painful, but does not use medication | PK | All 20 | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 23 | K6a p.Ala463Pro | c.1387G>C | Known | Spontaneous | Somewhat painful | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 24 | K6a p.Thr464Pro | c.1390A>C | Known | Familial | Very painful, but does not use medication | PK | All 20 | Yes | Follicular hyperkeratosis | No |
| 25 | K6a p.Leu468Pro | c.1403T>C | Known | Spontaneous | Very painful, but does not use medication | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 26 | K6a p.Leu469Pro | c.1406T>C | Known | Familial | Often requires medication to handle the pain | PPK | All 20 | Yes | Steatocystoma, pilosebaceous | No |
| 27 | K6a p.Leu469Pro | c.1406T>C | Known | Spontaneous | Often requires medication to handle the pain | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 28 | K6a p.Glu472Lys | c.1414G>A | Known | Spontaneous | Not painful (under 3 years) | PK | All 20 | No | Small red bumps and occasional spots on his face, but they could be standard baby acne | No |
| 29 | K6a p.Glu472Lys | c.1414G>A | Known | Spontaneous | Very painful, but does not use medication | PPK | All 20 | Yes | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 30 | K6a p.Glu473GlyfsTer91 | c.1417dupG | Unreported | Spontaneous | Somewhat painful | PPK | 10 fingernails, 7 toenails | Yes | NA | No |
| 31 | ND | c.1460–1G>C | Unreported | Familial | Often requires medication to handle the pain | PPK | 2 fingernails, 10 toenails | No | NA | No |
| 32 | K6b p.Asn172del | c.516_518delCAA | Known | Familial | Somewhat painful | PK | 10 fingernails, 7 toenails | Yes | NA | No |
| 33 | K6b p.Asn172del | c.516_518delCAA | Known | Familial | Very painful, but does not use medication | PPK | 6 fingernails, 10 toenails | Yes | Steatocystoma, pilosebaceous | No |
| 34 | K6b p.Asn172del | c.516_518delCAA | Known | Familial | Very painful, but does not use medication | PK | 6 fingernails, 10 toenails | No | Pilosebaceous, follicular hyperkeratosis | No |
| 35 | K6b p.Asn172del | c.516_518delCAA | Known | Familial | Somewhat painful | PPK | 8 fingernails, 10 toenails | No | Pilosebaceous, follicular hyperkeratosis | No |
| 36 | K6bGlu461Lys | c.1381G>A | Known | Spontaneous | Very painful, but does not use medication | PPK | 7 toenails | Yes | Follicular hyperkeratosis | No |
| 37 | K6b p.Leu469Arg | c.1406T>G | Unreported | Spontaneous | Somewhat painful | PK | 6 toenails | Yes | Follicular hyperkeratosis | No |
| 38 | K6b p.Glu472Lys | c.1414G>A | Known | Spontaneous | Very painful, but does not use medication | PK | 8 toenails | Yes | NA | No |
| 39 | K6b p.Glu472Lys | c.1414G>A | Known | Familial | Somewhat painful | PK | 4 toenails | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 40 | K6b p.Glu472Lys | c.1414G>A | Known | Spontaneous | Very painful, but does not use medication | PPK | 9 toenails | No | Steatocystoma | No |
| 41 | K6c p.Glu472Lys | c.1414G>A | Known | Familial | Very painful, but does not use medication | PPK | 4 toenails | Yes | Steatocystoma, pilosebaceous | No |
| 42 | K6c p.Glu472Lys | c.1414G>A | Known | Familial | Somewhat painful | PK | 2 toenails | No | NA | No |
| 43 | K16 p.Met121Lys | c.362T>A | Known | Familial | Very painful, but does not use medication | PPK | All 20 | No | NA | No |
| 44 | K16 p.Met121Thr | c.362T>C | Known | Spontaneous | Very painful, but does not use medication | PK | 4 toenails | No | NA | No |
| 45 | K16 p.Leu124His | c.371T>A | Known | Familial | Very painful, but does not use medication | PPK | 6 fingernails, 10 toenails | No | NA | No |
| 46 | K16 p.Leu124His | c.371T>A | Known | Familial | Very painful, but does not use medication | PPK | 5 toenails | No | NA | No |
| 47 | K16 p.Asn125Asp | c.373A>G | Known | Familial | Very painful, but does not use medication | PPK | 10 toenails | No | Pilosebaceous | No |
| 48 | K16 p.Asn125Ser | c.374A>G | Known | Spontaneous | Very painful, but does not use medication | PPK | All 20 | No | NA | No |
| 49 | K16 p.Asn125Ser | c.374A>G | Known | Spontaneous | Somewhat painful; only 6 years old | PK | 2 toenails | No | NA | No |
| 50 | K16 p.Asn125Ser | c.374A>G | Known | Familial | Very painful, but does not use medication | PPK | 3 toenails | Yes | NA | No |
| 51 | K16 p.Asn125Ser | c.374A>G | Known | Familial | Somewhat painful | PPK | 8 toenails | No | NA | No |
| 52 | K16 p.Asn125Ser | c.374A>G | Known | Spontaneous | Somewhat painful | PPK | 2 toenails | No | Follicular hyperkeratosis | No |
| 53 | K16 p.Asn125Ser | c.374A>G | Known | Familial | Often requires medication to handle the pain | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 54 | K16 p.Arg127Pro | c.380G>C | Known | Familial | Somewhat painful | PPK | All 20 | No | Follicular hyperkeratosis | No |
| 55 | K16 p.Arg127Gly | c.379C>G | Unreported | Familial | Very painful, but does not use medication | PPK | All 20 | No | Steatocystoma | No |
| 56 | K16 p.Arg127Cys | c.379C>T | Known | Familial | Often requires medication to handle the pain | PK | 5 toenails | No | Follicular hyperkeratosis | No |
| 57 | K16 p.Arg127Cys | c.379C>T | Known | Familial | Very painful, but does not use medication | PPK | 2 toenails | Yes | NA | No |
| 58 | K16 p.Arg127Cys | c.379C>T | Known | Familial | Very painful, but does not use medication | PPK | 3 toenails | No | NA | No |
| 59 | K16 p.Arg127Cys | c.379C>T | Known | Familial | Very painful, but does not use medication | PPK | None | No | NA | No |
| 60 | K16 p.Arg127Cys | c.379C>T | Known | Familial | Very painful, but does not use medication | PK | 6 toenails | No | NA | No |
| 61 | K16 p.Arg127Ser | c.379C>A | Unreported | Familial | Often requires medication to handle the pain | PK | 7 toenails | No | NA | No |
| 62 | K16 p.Arg127His | c.381G>A | Unreported | Familial | Very painful, but does not use medication | PPK | 4 toenails | Yes | Pilosebaceous, follicular hyperkeratosis | No |
| 63 | K16 p.Ser130del | c.389–391delCCT | Known | Familial | Often requires medication to handle the pain | PPK | All 20 | No | Follicular hyperkeratosis | No |
| 64 | K16 p.Leu132Pro | c.395T>C | Known | Familial | Very painful, but does not use medication | PPK | All 20 | No | NA | No |
| 65 | K16 p.Arg418Pro | c.1253G>C | Unreported | Familial | Very painful, but does not use medication | PK | 2 toenails | No | NA | No |
| 66 | K16 p.Arg418_Arg419del | c.1253_1258delGCCGCC | Unreported | Familial | Very painful, but does not use medication | PPK | 2 fingernails, 3 toenails | Yes | NA | No |
| 67 | K17 p.Met88Lys | c.263T>A | Known | Spontaneous | NA | None (under 3 years of age) | All 20 | No | Follicular hyperkeratosis | Yes |
| 68 | K17 p.Met88Arg | c.263T>G | Unreported | Spontaneous | Very painful, but does not use medication | PPK | 8 fingernails, 10 toenails | Yes | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 69 | K17 p.Asn90_Asp93delinsIle | c.269_278del10insT | Unreported | Familial | Very painful, but does not use medication | PPK | All 20 | No | Follicular hyperkeratosis | No |
| 70 | K17 p.Leu91Pro | c.272T>C | Unreported | Spontaneous | Very painful, but does not use medication | PPK | All 20 | No | Steatocystoma, follicular hyperkeratosis | No |
| 71 | K17 p.Asn92Ser | c.275A>G | Known | Familial | Very painful, but does not use medication | PK | All 20 | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | Yes |
| 72 | K17 p.Asn92Ser | c.275A>G | Known | Familial | Not painful | PPK | 6 fingernails, 10 toenails | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | Yes |
| 73 | K17 p.Asn92Ser | c.275A>G | Known | Spontaneous | Not painful | PPK | 6 fingernails, 10 toenails | No | Steatocystoma, pilosebaceous | Yes |
| 74 | K17 p.Asn92Ser | c.275A>G | Known | Spontaneous | Often requires medication to handle the pain | PK | 10 fingernails, 8 toenails | Yes | Pilosebaceous | No |
| 75 | K17 p.Asn92Ser | c.275A>G | Known | Spontaneous | NA | None (under 3 years of age) | All 20 | No | NA | Yes |
| 76 | K17 p.Asn92Ser | c.275A>G | Known | Familial | Somewhat painful | PPK | 6 fingernails, 2 toenails | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | Yes |
| 77 | K17 p.Asn92Ser | c.275A>G | Known | Familial | Often requires medication to handle the pain | PPK | 2 fingernails, 10 toenails | No | Pilosebaceous, follicular hyperkeratosis | Yes |
| 78 | K17 p.Arg94Ser | c.280C>A | Unreported | Familial | Very painful, but does not use medication | PK | 3 toenails | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 79 | K17 p.Arg94Cys | c.280C>T | Known | Familial | Very painful, but does not use medication | PPK | 4 toenails | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | No |
| 80 | K17 p.Arg94Cys | c.280C>T | Known | Familial | Not painful | NA | 1 toenail | No | Steatocystoma | Yes |
| 81 | K17 p.Leu95Pro | c.284T>C | Known | Spontaneous | NA; under 2 years old | NA; under 2 years old | All 20 | No | NA | Yes |
| 82 | K17 p.Leu95Pro | c.284T>C | Known | Familial | Very painful, but does not use medication | PK | All 20 | No | Pilosebaceous | Yes |
| 83 | K17 p.Leu99Pro | c.296T>C | Known | Familial | Somewhat painful | PPK | All 20 | Yes | Follicular hyperkeratosis | No |
| 84 | K17 p.Leu99Pro | c.296T>C | Known | Spontaneous | Very painful, but does not use medication | PPK | All 20 | No | Steatocystoma, pilosebaceous, follicular hyperkeratosis | Yes |
PK, plantar keratoderma; PPK, palmoplantar keratoderma; NA, not applicable; ND, not determined (protein consequences of a splice site mutation not known with certainty).