Table 1.
Summary of Mitf mutations in WS and TS and melanomas used in this study
| Mutation | Location | Disease | Authors | Phenotype/remarks | Inheritance |
|---|---|---|---|---|---|
| E87R | AD | Melanoma | Cronin et al. (16) | Metastatic melanomas with BRAF (V600E) mutation | Somatic |
| L135V | AD | Melanoma | Cronin et al. (16) | Metastatic melanomas | Somatic |
| L142F | AD | Melanoma | Cronin et al. (16) | Metastatic melanomas | Somatic |
| R203K | BR | WS2 | Tassabehji et al. (5) | Typical WS2. Mutation found in proband does not segregate with disease | Neutral variant |
| K206Q | BR | WS2 | Leger et al. (12) | 36-year female; SNHL, white forelock blue irides | Familial |
| N210K | BR | Tietz | Smith et al. (10) | Deafness, blonde hair, white eyelashes & eyebrows, cutaneous hypopigmentation | Familial |
| I212M | BR | Tietz/WS2 | Welch et al. (43) | Blue eyes, hypopigmentation of hair and skin, 14 of 28 affected members have SNHL | Familial |
| I212S | BR | WS2 | Leger et al. (12) | 9-year male; generalized hypopigmentation, freckles, blue irides, premature graying | Familial |
| E213D | BR | WS2 | Leger et al. (12) | 33-year female; SNHL, white forelock, premature graying, blue irides | De novo |
| R214X | BR | WS2 | Lalwani et al. (42) | SNHL, heterochromia of the irides, premature graying, white forelock, a three-generation WS2 family | Familial |
| - | - | WS2 | Nobukuni et al. (40) | SNHL, heterochromia of the irides, white forelock, early graying | Familial |
| R216K | BR | WS2 | Leger et al. (12) | 21-year female; SNHL, white forelock, fair skin, blue irides | De novo |
| R217del | BR | Tietz | Leger et al. (12) | 3-year female; SNHL, generalized hypopigmentation, blue irides | Familial |
| - | - | WS2 | Chen et al. (41) | Three affected families | Familial |
| - | - | Tietz | Tassabehji et al. (5) | SNHL, blonde/red hair color, pale skin, blue irides; dominant pedigree | Familial |
| -l | - | Tietz | Shigemura et al. (11) | 15-year male, generalized hypopigmentation, blue irides, blonde hair and eyebrows | Familial |
| R217I | BR | Tietz | Léger et al. (12) | 3-year female; SNHL, generalized hypopigmentation, blue irides and white forelock | Familial |
| - | - | WS2 | Chen et al. (41) | SNHL, blue irides, premature graying | De novo |
| R217G | BR | WS2 | Chen et al. (41) | No data available | n/a |
| I224S | HLH | WS2 | Pingault et al. (9) | 6-year female; SNHL, white forelock, heterochromia of the irides | Familial |
| G244R | HLH | Melanoma | Cronin et al. (16) | Metastatic melanomas with BRAF (V600E) mutation | Somatic |
| S250P | HLH | WS2 | Tassabehji et al. (5) | Female patient; unilateral hearing loss, premature graying | Familial |
| Y253C | HLH | WS2 | Read et al. (8) | No data available | n/a |
| R259X | HLH | WS2 | Nobukuni et al. (40) | SNHL, heterochromia of the irides, white forelock, early graying | Familial |
| N278D | ZD | WS2 | Tassabehji et al. (5) | Female patient; SNHL, inherited from unaffected father | Familial |
| L283P | ZD | WS2 | This study | 30-year female; SNHL, heterochromia of the irides | Familial |
| S298P | AD | WS2 | Tassabehji et al. (5) | Affected patient comes from a three-generation history of WS2 | Neutral variant |
| E318K | AD | Melanoma | Bertolotto et al. (17) | Five of 62 melanoma and renal cell carcinoma patients harbor the E318K mutation | Germline |
| D380N | AD | Melanoma | Cronin et al. (16) | Metastatic melanomas with a BRAF (V600E) mutation | Somatic |
AD, activation domain; BR, basic region; HLH, helix–loop–helix; ZD, zipper domain; SNHL, sensorineural hearing loss, n/a not available.