Identification of three patients with a very mild form of Smith-Lemli-Opitz syndrome.
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.
Langius
Fernanda A A
FA
Department of Metabolic Diseases, Utrecht, The Netherlands.
Waterham
Hans R
HR
Romeijn
Gerrit Jan
GJ
Oostheim
Wendy
W
de Barse
Martina M J
MM
Dorland
Lambertus
L
Duran
Marinus
M
Beemer
Frits A
FA
Wanders
Ronald J A
RJ
Poll-The
Bwee Tien
BT
D000293:Adolescent; D002648:Child; D002775:Cholestadienols / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004252:DNA Mutational Analysis; D003684:Dehydrocholesterols / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency* / Q000235:genetics; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics / Q000503:physiopathology*
D002775:Cholestadienols; D003684:Dehydrocholesterols; C026359:cholesta-5,8-dien-3 beta-ol; D002784:Cholesterol; C016705:7-dehydrocholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase