PNPLA1 and recently SDR9C7 and SULT2B1. 1–6 Furthermore, seven patients from a large consanguineous family were described as having ARCI resulting from a homozygous mutation in LIPN; 7 however, the first symptoms did not appear until the age of 5 years and the criterion of a congenital form of ichthyosis was not fulfilled. In this study, we report the clinical and molecular findings for seven patients with ARCI who carried five previously unreported mutations in SDR9C7. We could identify homozygous mutations in SDR9C7 using whole-exome sequencing in three patients belonging to two families (P1-1, P1-2, P2). A subsequent screening of genetically unsolved ARCI cases revealed four additional patients (P3–P6) with mutations in SDR9C7 (reference sequence NM_148897. 2). All seven patients showed a relatively mild ichthyosis phenotype with generalized dry and scaly skin and mild or local erythema (Fig. 1). With one exception (P2), the patients were not born as collodion babies (CBs). In one case (P3), the ichthyosis phenotype first appeared at the age of 6 months. In three patients (P2, P3, P4) keratoderma of the feet and/or hands was observed; P3 showed only a mild palmar hyperkeratosis. Three further patients (P1-1, P1-2, P6) presented hyperlinearity of the palms and soles. Erythema was present in most of our patients, but only at birth or in mild and local forms. Fungal infections were frequent in three patients (P1-1, P1-2, P3). Anhidrosis was observed in four patients (P2, P3, P4, P6), while two patients (P1-1, P1-2) had no problems related to sweating. Two patients (P3, P6) had swollen hands, feet or legs.

The mutation c. 112G> A (p. Gly38Arg, rs764593071), which we found in three families (homozygous in P1-1/P1-2, heterozygous in P4, P6), is located in the motif Thr-Gly-XXX-Gly-X-Gly in SDR9C7 and corresponds to the last glycine. This highly conserved region is important for the maintenance of the central b-sheet, which is essential for cofactor binding, 8 suggesting a strong functional impairment of SDR9C7 in these patients. In P4 and P6, we identified the heterozygous