Correspondence PIEBALDISM IN DIAMOND–BLACKFAN ANAEMIA: A NEW PHENOTYPE? Piebaldism is a rare autosomal dominant disorder char- acterized by a defect in pigmentation revealed as bilateral but non-symmetrical white patches of hair and skin mostly affecting the face, the chest, the abdomen and the extremities, but never the back. The similar pigmentation phenotype of dominant White spotting mice (Geissler et al, 1988) and human piebaldism enabled the characteriza- tion of the gene responsible for the piebald trait in both species. c-kit gene was found mutated and associated with piebaldism in both human and mice (Reith et al, 1990). Although mutations in stem cell factor (SCF) gene in Steel (Sl) mice (Copeland et al, 1990) reproduce the dominant White spotting mice phenotype, to date, no mutation in SCF gene has been identified in human piebaldism. While piebaldism in human is the only clinical manifestation reported in association with mutations in the c-kit gene, in the mouse, haematopoiesis and gametogenesis are also affected to varying levels depending both on the nature of mutation in c-kit gene and on the homozygosity or heterozygosity of the mutation (Reith et al, 1990). Dom- inant White spotting (W) and Steel (Sl) mice (Geissler et al, 1988) exhibit mild to severe macrocytic anaemia, reticulocytopenia, and normal platelet and granulocyte counts, which are phenotypic anomalies similar to those observed in Diamond–Blackfan anaemia (DBA). Extensive studies failed to reveal mutations in either the c-kit gene or its ligand SCF in association with DBA phenotype (Spritz & Freedman, 1993). However, recent studies have identified mutations in the ribosomal protein S19 (RPS19) gene in 25% of patients affected by DBA (Willig et al, 1999), and a yet to be characterized gene on chromo- some 8p has been also linked to DBA phenotype (Gazda et al, 2001). With the identification in the French DBA registry of a patient carrying piebaldism, we wondered whether a mutation in the c-kit gene could explain both the piebald trait and erythroblastopenia or if piebaldism was part of the DBA phenotype. To distinguish between these two alternatives, we sequenced all 21 exons of c-kit gene and all nine exons of SCF gene. Our failure to document any mutation in either the c-kit gene or in the SCF gene implies that other gene defects are responsible for both DBA and piebaldism phenotypes in our patient, and piebaldism was not related to a mutation in c-kit or SCF genes. Although we could not eliminate a neo- mutation, another argument in favour of this conclusion is the fact that our patient is the only one in his family to carry a piebald trait despite the known autosomal dominant inheritance of piebaldism. This finding, which to our knowledge is the first such case described in DBA, extends piebaldism as a potential feature associated with DBA. Lydie D. A. Costa 1 Jason Fixler 1 Olivier Berets 2 Thierry Leblanc 3 Thiebaut-Noel Willig 1 Narla Mohandas 4 Gil Tchernia 5 1 Lawrence Berkeley National Laboratory, Life Science Division, Berkeley, CA, USA, 2 Service de me ´decine interne, Ho ˆpital d’instruction des arme ´es Percy, Clamart, France, 3 Service d’he ´matologie pe ´diatrique, Ho ˆpital Saint-Louis, France, 4 New York Blood Center, New York, NY, USA, and 5 Laboratoire d’he ´matologie, AP-HP et faculte ´ de me ´decine Paris Sud, Ho ˆpital Bice ˆtre, Le Kremlin Bice ˆtre, France. E-mail: mnarla@nybc.org REFERENCES Copeland, N.G., Gilbert, D.J., Cho, B.C., Donovan, P.J., Jenkins, N.A., Cosman, D., Anderson, D., Lyman, S.D. & Williams, D.E. (1990) Mast Cell Growth Factor maps near the Steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell, 63, 175–183. Gazda, H., Lipton, J.M., Willig, T.N., Ball, S., Niemeyer, C.M., Tchernia, G., Mohandas, N., Daly, M.J., Ploszynska, A., Orfali, K.A., Vlachos, A., Glader, B.E., Rokicka-Milewska, R., Ohara, A., Baker, D., Pospisilova, D., Webber, A., Viskochil, D.H., Nathan, D.G., Beggs, A.H. & Sieff, C.A. (2001) Evidence for linkage of familial Diamond–Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. Blood, 97, 2145–2150. Geissler, E.N., Ryan, M.A. & Housman, D.E. (1988) The dominant- white spotting (W) locus of the mouse encodes the c-kit proto- oncogene. Cell, 55, 185–192. Reith, A.D., Rottapel, R., Giddens, E., Brady, C., Forrester, L. & Bernstein, A. (1990) W mutant mice with mild or severe devel- opmental defects contain distinct point mutations in the kinase domain of the c-kit receptor. Genes and Development, 4, 390–400. Spritz, R.A. & Freedman, M.H. (1993) Lack of mutations of the MGF and KIT genes in Diamond–Blackfan anemia. Blood, 81, 3165. Willig, T.N., Draptchinskaia, N., Dianzani, I., Ball, S., Niemeyer, C., Ramenghi, U., Orfali, K., Gustavsson, P., Garelli, E., Brusco, A., Tiemann, C., Perignon, J.L., Bouchier, C., Cicchiello, L., Dahl, N., Mohandas, N. & Tchernia, G. (1999) Mutations in ribosomal protein S19 gene and Diamond Blackfan anemia: wide variations in phenotypic expression. Blood, 94, 4294–4306. Keywords: Diamond–Blackfan anaemia, piebaldism, c-kit, SCF. 572 Ó 2002 Blackwell Publishing Ltd British Journal of Haematology, 2002, 119, 572–580