A novel mutation of the DHCR7 gene in a sicilian compound heterozygote with Smith-Lemli-Opitz Syndrome.
BACKGROUND
Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis, resulting from deficient 7-dehydrocholesterol reductase (3beta-hydroxysterol Delta7-reductase) activity, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. SLOS is most common among people of European descent, with a reported incidence of 1 per 20,000-60,000 newborns, depending on the diagnostic criteria and the reference population. More than 80 different mutations have been identified in several hundred patients. In Italy, SLOS appears to be a rare condition, probably because of underdiagnosis.


METHODS
We analyzed by direct sequencing the 7-dehydrocholesterol reductase gene (DHCR7) in a Sicilian patient with Smith-Lemli-Opitz syndrome and his parents in order to characterize the molecular defect.


RESULTS
The molecular analysis of the coding exons and the intron-exon boundaries of the DHCR7 gene demonstrated the presence of two missense mutations: a novel mutation (I251N) and a known mutation (E288K) responsible in a compound heterozygous state for a severe form of SLOS.


CONCLUSIONS
The present study describes a Sicilian patient, a carrier of a novel mutation of the DHCR7 gene (I251N), which is responsible in a compound heterozygous state for a severe form of SLOS.
Romano
Fabrizio
F
Department of Biomedical Sciences, Section of Clinical Pathology and Molecular Oncology, University of Catania, Catania, Italy.
Fiore
Barbara
B
Pezzino
Franca Maria
FM
Longombardo
Maria Teresa
MT
Cefalù
Angelo Baldassare
AB
Noto
Davide
D
Puglisi
Ambra
A
Brogna
Alfio
A
Mattina
Teresa
T
Averna
Maurizio
M
Travali
Salvatore
S
D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D020125:Mutation, Missense; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D010375:Pedigree; D012802:Sicily; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics*
D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase