Mutations in the NSDHL gene, encoding a 3 beta-hydroxysteroid dehydrogenase, cause CHILD syndrome

We report for the first time that CHILD syndrome:(MIM 308050), an X-linked dominant, male-lethal trait characterized by an inflammatory nevus with str iking lateralization and strict midline demarcation, as well as ipsilateral hypoplasia of the body is caused by mutations in the gene NSDHL located at Xq28 (NAD(P)H steroid dehydrogenase-like protein) encoding a 3 beta-hydrox ysteroid dehydrogenase functioning in the cholesterol biosynthetic pathway. SSCA and genomic sequence analysis of NSDHL identified in 6 patients with CHILD syndrome, including one boy as well as a mother and her daughter, mut ations potentially impairing protein function, This phenotype is distinct f rom, but shares various clinical and biochemical findings with chondrodyspl asia punctata (CDPX2, MIM 302960), CDPX2 is due to mutations affecting a De lta 8-Delta 7 sterol isomerase (EBP, emopamil binding protein, at Xp11.22 - p11.23) that functions downstream of NSDHL in a later step of cholesterol biosynthesis. EBP was unaffected in the patients analyzed by us demonstrati ng that CHILD syndrome and CDPX2 are not caused by allelic mutations. Two: mouse X-linked dominant male-lethal traits, bare patches (Bpa) and striated (Str) ha previously been associated with mutations in Nsdhl, They provide animal models for the study of CHILD syndrome, a further human condition du e to mutations in a gene of the cholesterol synthesis pathway.