A patient with Smith-Lemli-Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement.
BACKGROUND
The Smith-Lemli-Opitz (SLO) syndrome is a multiple congenital anomaly with mental retardation due to a decreased or lack of activity of 7-dehydrocholesterol reductase as a consequence of mutations of the DHCR7 gene. This paper describes a special patient with SLO syndrome. Laboratory examination showed low cholesterol (2.77 mmol/L) and increased 7-dehydrocholesterol level (102 mg/L). Molecular genetic analysis revealed a compound heterozygosity c.964-1G>C/p.G366V (c.G1370T) of the proband. The p.G366V is a novel mutation of the DHCR7 gene with guanine by thymine nucleotide exchange resulting in glycin by valin amino acid exchange in the dehydrocholesterol reductase enzyme. Simvastatin (0.2 mg/kg/day) and cholesterol replacement therapy (150-250 mg/kg/day) led to significant improvement in the patient's laboratory findings (7-dehydrocholesterol, cholesterol) as well as in his behavior and gross motor function.


CONCLUSIONS
Our patient demonstrates that the c.964-1G>C/p.G366V (c.G1370T) genotype of combined heterozygosity is associated with a typical form of SLO syndrome along with moderately altered laboratory findings and a favorable biochemical response to cholesterol and simvastatin treatment.
Szabó
Gabriella P
GP
Pediatrics Department, Medical and Health Science Center, Debrecen University, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
Oláh
Anna V
AV
Kozak
Libor
L
Balogh
Erzsébet
E
Nagy
Andrea
A
Blahakova
Ivona
I
Oláh
Eva
E
D002648:Child; D002784:Cholesterol / Q000097:blood / Q000172:deficiency; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000097:blood / Q000235:genetics*; D019821:Simvastatin / Q000008:administration & dosage*; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood / Q000188:drug therapy / Q000235:genetics*
D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D004247:DNA; D002784:Cholesterol; D019821:Simvastatin; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase