Smith-Lemli-Opitz syndrome: Deficient Delta 7-reductase activity in cultured skin fibroblasts and chorionic villus fibroblasts and its application to pre- and postnatal detection

The Smith-Lemli-Opitz syndrome (SLO) is a recently identified disorder of cholesterol biosynthesis, clinically characterized by typical facial dysmorphia including microcephaly, ptosis, cataracts, anteverted nares, low-set posteriorly rotated ears and micrognathia, multiple congenital limb and organ anomalies and severe mental retardation with incomplete myelination of the brain and peripheral nerves (Smith et al 1964). In 1993, Irons and coworkers (1993) reported the marked elevation of 7-dehydrocholesterol in patients with SLO, suggesting a defect in the penultimate step of cholesterol biosynthesis (Tint et al 1994). This was established experimentally by the same group of investigators, who reported deficient 7-dehydrocholesterol Δ 7 -reductase activity in microsomes prepared from liver specimens obtained from four SLO homozygotes (Shafer et al 1995). These experiments were followed by studies in cultured skin fibroblasts using radiolabelled lathosterol as a more stable precursor (Honda et al 1995). Similar experiments were performed by Lund and coworkers (1996) also using [ 3 H]lathosterol. In this paper we describe a simple method allowing direct measurement of 7-dehydrocholesterol Δ 7 -reductase activity in cultured skin fibroblasts and chorionic villus fibroblasts using radiolabelled 7-dehydrocholesterol which is now commercially available.