Netherton syndrome, SPINK5, LEKTI Netherton syndrome (NS) is an autosomal recessive disorder characterized by congenital ichthyosis and severe atopic manifestations. A specific hair shaft defect ('bamboo hair') is diagnostic for the disease. The genetic defect in NS is caused by mutations in the SPINK5 gene that encodes a serine protease inhibitor LEKTI (lympho-epithelial Kazal-type related inhibitor). The phenotype of the patients can vary considerably in severity, and can fluctuate over time in individual patients. The aim of the work presented here is part of an effort to correlate the clinical phenotype of our patients with NS with their genotype. To this end, the 33 exons, and flanking parts of the introns, were PCR amplified and sequenced. In six of the eight patients studied, two mutations could be identified in each patient, a result that is expected for an autosomal recessive disease. Four of these are homozygotes, probably because of consanguinity of the parents: two carry a nonsense mutation, one patient a frameshift mutation and one a splice site mutation. The other 2 patients are compound heterozygotes for two splice site mutations, or for a splice site and a frameshift mutation. In the two remaining patients only one (a splice site mutation) or no mutation could be found. Phenotypic data are being collected from these patients, and these data will be compared to the type and position of the mutations present.