IDENTIFICATION OF A YEAST ARTIFICIAL CHROMOSOME CLONE SPANNING A TRANSLOCATION BREAKPOINT AT 7Q32.1 IN A SMITH-LEMLI-OPITZ SYNDROME PATIENT

Smith-Lemli-Opitz syndrome (SLOS) is a mental retardation/multiple con genital anomaly syndrome. The gene(s) involved has not been mapped or cloned, but, recently, a biochemical abnormality in cholesterol biosyn thesis has been shown to occur in most SLOS patients. The defect is su spected to occur in the penultimate step of the cholesterol pathway, i nvolving the enzyme 7-dehydrocholesterol reductase, which has not been isolated. On the basis of the hypothesis that a de novo balanced tran slocation [t(7;20)(q32.1; q13.2)] in an SLOS patient directly interrup ts the SLOS gene, positional cloning techniques are being employed to localize and identify the SLOS gene. We report the identification of a chromosome 7-specific YAC that spans the translocation breakpoint, as detected by FISH. This is the first study narrowing a candidate SLOS region and placing it on physical and genetic maps of the human genome .