Mutation analysis of the DKC1 gene in incontinentia pigmenti

Editor—There are a number of monogenic diseases with complex phenotypes which are clinically distinct but also overlap in phenotype with one or more other syndromes. If mutations in the same gene are responsible for causing the related syndromes, the diseases are allelic. Two diseases linked to Xq28, incontinentia pigmenti (IP, MIM 308310, Bloch-Sulzberger syndrome) and dyskeratosis congenita (DKC, MIM 305000, Zinsser-Cole-Engmann syndrome) show similarities in phenotype, although the modes of expression differ. Whereas IP is X linked dominant with embryonic lethality in males, the major form of DKC is X linked recessive. The gene responsible for causing DKC, DKC1 , was recently identified1and maps about 20 kb proximal to the factor VIII gene, F8C. 2 Linkage analyses have provided evidence that the IP gene is located in the telomeric 2 Mb region of Xq28 distal to DXS523 and lod scores of highest significance were found around F8C. 4 5 The physical map position of DKC1 and genetic linkage of the IP locus, together with the overlap in the DKC and IP phenotypes (table1), raised the possibility that these two diseases could be allelic. View this table: Table 1 Comparison of the IP and DKC phenotypes affecting ectodermal tissues and the haemopoietic system The IP and DKC phenotypes share abnormalities in ectodermal derivatives, such as nail dystrophy, alopecia, hypodontia, and skin manifestations6 7 (table 1). Both IP and DKC are characterised by the early appearance of reticulate skin pigmentation, although this manifests differently in the two diseases. In IP the clinical signs affecting the skin are initially apparent as an erythematous, inflammatory vesicular rash. The rash later becomes verrucous and streaks of hyperpigmentation follow. …