Molecular studies in Portuguese patients with Smith-Lemli-Opitz syndrome and report of three new mutations in DHCR7

M. L. Cardoso, A. Balreira, E. Martins, L. Nunes, A. Cabral, M. Marques, M. Reis Lima, J. S. Marques, A. Medeira, I. Cordeiro, S. Pedro, M. C. Mota, C. Dionisi-Vici, F. M. Santorelli, C. Jakobs, P. T. Clayton, L. Vilarinho

Research output: Contribution to journalArticlepeer-review

Abstract

Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterised by craniofacial dysmorphism, mental retardation, multiple congenital anomalies, and increased levels of 7-dehydrocholesterol (7-DHC) in body tissues and fluids. SLO is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, the last enzyme of cholesterol biosynthesis pathway. In our investigation, we screened 682 dysmorphic/mentally retarded Portuguese patients for abnormal levels of 7-DHC in blood by UV spectrometry. We identified six unrelated patients with SLO (0.87% of total). Mutational analysis of the DHCR7 gene led to the identification of seven distinct mutations, three of which are new (F174S, H301R, and Q98X). The common IVS8-1G > C and T93M variants together with the H301R accounted for 70% of the all SLO alleles in our population. Our findings contribute to the variegate array of pathological changes in the DHCR7 gene among different European populations.

Original languageEnglish
Pages (from-to)228-235
Number of pages8
JournalMolecular Genetics and Metabolism
Volume85
Issue number3
DOIs
Publication statusPublished - Jul 2005

Keywords

  • 7-Dehydrocholesterol
  • DHCR7 gene
  • Dysmorphy
  • Hypocholesterolemia
  • Metabolic disorder
  • Screening
  • SLO
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

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