Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G-->C genotype.
Smith-Lemli-Opitz syndrome (RHS) (SLOS, OMIM 270400) is an autosomal recessive disorder of cholesterol biosynthesis caused by mutations of the 3beta-hydroxysterol Delta(7)-Delta(8)-reductase gene, DHCR7. We report a fetus with holoprosencephaly and multiple congenital anomalies who was homozygous for the IVS8-1G-->C mutation. Following termination of pregnancy, both the elevated amniotic fluid 7-dehydrocholesterol level and the DHCR7 mutations were demonstrated. Two other newborn infants with IVS8-1G-->C/IVS8-1G-->C genotype are described. This report illustrates a severe phenotypic extreme of SLOS associated with a null genotype, underscores the complex relationship between SLOS and holoprosencephaly, and discusses the possible pathogenetic mechanisms of the development of holoprosencephaly in SLOS.
Nowaczyk
M J
MJ
Department of Pathology and Molecular Medicine, McMaster University, Canada. nowaczyk@hhsc.ca
Farrell
S A
SA
Sirkin
W L
WL
Velsher
L
L
Krakowiak
P A
PA
Waye
J S
JS
Porter
F D
FD
D001483:Base Sequence; D017809:Fatal Outcome; D005313:Fetal Death; D005333:Fetus; D005838:Genotype; D016142:Holoprosencephaly / Q000473:pathology; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010088:Oxidoreductases / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors; D017354:Point Mutation; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics* / Q000473:pathology
D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase