KITLG Mutations Cause Familial Progressive Hyper- and Hypopigmentation Mustapha Amyere, Thomas Vogt, Joe Hoo, Flemming Brandrup, Anette Bygum, Laurence Boon, Miikka Vikkula  Journal of Investigative Dermatology  Volume 131, Issue 6, Pages 1234-1239 (June 2011) DOI: 10.1038/jid.2011.29 Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Familial progressive hyper- and hypopigmentation in seven families. Five families (A–E) from southeastern Germany; family F, USA; family G, Denmark. Numbered individuals included in whole-genome mapping. Black symbols, familial progressive hyper- and hypopigmentation. Journal of Investigative Dermatology 2011 131, 1234-1239DOI: (10.1038/jid.2011.29) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Clinical features of family G. (a) Boy, 11 years of age, with general hyperpigmentation, accentuated in the neck, with scattered café-au-lait macules, lentigines, and small hypopigmented spots. (b) Male, 43 years of age, with vitiligo as a rim in the periphery of a dark brown macule at the inner aspect of left knee. Journal of Investigative Dermatology 2011 131, 1234-1239DOI: (10.1038/jid.2011.29) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Multipoint linkage analysis on three familial progressive hyper- and hypopigmentation families. (a) Combined pedigree for families A+B considering closest possible common ancestor; (b) z-score plots for families A+B (locus: (66295754–94584860); (c, d) family F (locus: (70153597–114764214) and family G (locus: (58300374–99949424). X axis, physical position on 12q in megabases (Mb); y axis, nonparametric z-score. Whole-genome scan using Affymetrix 10K arrays (families A+B) and 250K arrays for families F and G. Journal of Investigative Dermatology 2011 131, 1234-1239DOI: (10.1038/jid.2011.29) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Mutations found in KITLG. Mutations c.98T>C and c.100A>C, resulting in substitutions of p.Val33Ala and p.Thr34Pro in families F and G, respectively. In families A and B, c.107A>G substitution resulting in p.Asn36Ser change. N, position of mutation. Journal of Investigative Dermatology 2011 131, 1234-1239DOI: (10.1038/jid.2011.29) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 KITLG signalling pathway in melanogenesis and its role on skin pigmentation. DUH2, Dyschromatosis Universalis Hereditaria 2; ERK, extracellular signal-regulated kinase; FPHH, familial progressive hyper- and hypopigmentation; FPH, familial progressive hyperpigmentation; GDP, guanosine diphosphate; GTP, guanosine triphosphate; NF1, neurofibromin 1; RAL, retinaldehyde. Journal of Investigative Dermatology 2011 131, 1234-1239DOI: (10.1038/jid.2011.29) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions