title: Smith-Lemli-Opitz syndrome: evidence of T93M as a common mutation of delta7-sterol reductase in Italy and report of three novel mutations.
abstract: The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis characterised by facial dysmorphisms, mental retardation and multiple congenital anomalies. SLOS is caused by mutations of the human Delta7-sterol reductase (DHCR7) gene and, so far, 19 different mutations have been described. Among these, mutations impairing the activity of the C-terminus appear to be the most severe. Here we report the mutational analysis of the DHCR7 gene in nine Italian SLOS patients. The T93M mutation, previously reported in one patient, results the most frequent one (7/18 alleles) in our survey. Furthermore, we identified three novel mutations, two missense mutations (N407Y and E448K), and a 33 bp deletion spanning part of exon 5 and the donor splice site of intron 5.
authors.affiliation: Dipartimento di Pediatria, Università, Federico II.
authors.forename: D
authors.initials: D
authors.lastname: De Brasi
authors.forename: T
authors.initials: T
authors.lastname: Esposito
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.forename: G
authors.initials: G
authors.lastname: Parenti
authors.forename: M P
authors.initials: MP
authors.lastname: Sperandeo
authors.forename: A
authors.initials: A
authors.lastname: Zuppaldi
authors.forename: T
authors.initials: T
authors.lastname: Bardaro
authors.forename: M A
authors.initials: MA
authors.lastname: Ambruzzi
authors.forename: L
authors.initials: L
authors.lastname: Zelante
authors.forename: A
authors.initials: A
authors.lastname: Ciccodicola
authors.forename: G
authors.initials: G
authors.lastname: Sebastio
authors.forename: M
authors.initials: M
authors.lastname: D'Urso
authors.forename: G
authors.initials: G
authors.lastname: Andria
mesh_terms: D000293:Adolescent; D000483:Alleles; D002675:Child, Preschool; D002784:Cholesterol / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D005145:Face / Q000002:abnormalities; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D007558:Italy; D008297:Male; D020125:Mutation, Missense; D010088:Oxidoreductases / Q000235:genetics*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D010375:Pedigree; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*
chemical_list: C033144:lathosterol delta-5-dehydrogenase; D002784:Cholesterol; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors