TY - JOUR
T1 - Identification of three patients with a very mild form of Smith-Lemli-Opitz syndrome
AU - Langius, Fernanda A. A.
AU - Waterham, Hans R.
AU - Romeijn, Gerrit Jan
AU - Oostheim, Wendy
AU - de Barse, Martina M. J.
AU - Dorland, Lambertus
AU - Duran, Marinus
AU - Beemer, Frits A.
AU - Wanders, Ronald J. A.
AU - Poll-The, Bwee Tien
PY - 2003
Y1 - 2003
N2 - 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
AB - 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
U2 - https://doi.org/10.1002/ajmg.a.20207
DO - https://doi.org/10.1002/ajmg.a.20207
M3 - Article
C2 - 12949967
SN - 1552-4825
VL - 122A
SP - 24
EP - 29
JO - American journal of medical genetics. Part A
JF - American journal of medical genetics. Part A
IS - 1
ER -