Identification of three patients with a very mild form of Smith-Lemli-Opitz syndrome
| Autor: | Fernanda A.A. Langius, Ronald J.A. Wanders, Bwee Tien Poll-The, G. J. Romeijn, Martina M.J. de Barse, Frits A. Beemer, W. Oostheim, Marinus Duran, Lambertus Dorland, Hans R. Waterham |
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| Přispěvatelé: | Paediatric Metabolic Diseases, Laboratory Genetic Metabolic Diseases, Paediatric Neurology, Neurology |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Oxidoreductases Acting on CH-CH Group Donors Adolescent DNA Mutational Analysis Biology Compound heterozygosity 7-Dehydrocholesterol chemistry.chemical_compound Dehydrocholesterols Internal medicine medicine Humans Child Genetics (clinical) Cholesterol Cholestadienols Dysostosis Infant medicine.disease Null allele Smith-Lemli-Opitz Syndrome Hypocholesterolemia Endocrinology chemistry Smith–Lemli–Opitz syndrome Mutation testing Female lipids (amino acids peptides and proteins) |
| Zdroj: | American journal of medical genetics. Part A, 122A(1), 24-29. Wiley-Liss Inc. |
| ISSN: | 1552-4825 |
| Popis: | Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome characterized by mental retardation, congenital anomalies, and growth deficiency. The syndrome is caused by a block in cholesterol biosynthesis at the level of 7-dehydrocholesterol reductase (7-DHCR), which results in elevated levels of the cholesterol precursor 7-dehydrocholesterol (7-DHC) and its isomer 8-dehydrocholesterol (8-DHC). We report on three patients from two families with a very mild clinical presentation of SLOS. Their plasma cholesterol values were normal and their plasma levels of 7- and 8- DHC were only slightly elevated. In cultured skin fibroblasts, a significant residual 7-DHCR activity was found. All three patients were compound heterozygotes for a novel mutation affecting translation initiation (M1L). Two of them had the common IVS8-1G>C null mutation and the third patient an E448K mutation in the 7-DHCR gene. Our findings emphasize the importance of using a sensitive method for measuring precursors of cholesterol in combination with mutation analysis to analyze patients with only minimal clinical SLOS-like signs. |
| Databáze: | OpenAIRE |
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