Assignment of the gene for a new hereditary nail disorder, isolated congenital nail dysplasia, to chromosome 17p13

Isolated congenital nail dysplasia is an autosomal dominant disorder recent ly observed in a large family from southern Germany. The disorder is charac terized by longitudinal streaks, thinning, and impaired formation of the na il plates leading to increased vulnerability of the free nail margins. In m ost cases, all fingernails and toenails are similarly involved with some ac centuation of the thumb and great toenails. Histologic changes include hype rgranulosis of the nail matrix and epithelial outgrowths from the nail bed. Patients do not show any alterations of hair growth and dentition, no malf unction of sweat glands and sensory organs, and no skeletal abnormalities. Isolated congenital nail dysplasia manifests from the first year of life wi th variable expressivity. In order to localize chromosomally the gene under lying isolated congenital nail dysplasia, linkage to the known keratin gene cluster regions on chromosomes 12q12 and 17q21 was ruled out first. The an alysis of 150 microsatellite markers on various chromosomes mapped the isol ated congenital nail dysplasia gene to the 6 cM interval between markers at D17S926 and D17S1528 on chromosome 17p13. Markers at D17S849, D17S1840, an d D17S1529 co-segregated completely with the isolated congenital nail dyspl asia locus. The maximum two-point LOD score was found for the marker at D17 S1840 (Z(max) = 6.72 at Theta(max) = 0.00). The identified region harbors n o currently known genes involved in skin or nail abnormalities. Isolated co ngenital nail dysplasia probably represents a novel isolated defect of nail development. The localization of this gene is, therefore, the first step t owards the identification of a new factor in nail formation.