Molecular studies in Portuguese patients with Smith-Lemli-Opitz syndrome and report of three new mutations in DHCR7.
Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterised by craniofacial dysmorphism, mental retardation, multiple congenital anomalies, and increased levels of 7-dehydrocholesterol (7-DHC) in body tissues and fluids. SLO is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, the last enzyme of cholesterol biosynthesis pathway. In our investigation, we screened 682 dysmorphic/mentally retarded Portuguese patients for abnormal levels of 7-DHC in blood by UV spectrometry. We identified six unrelated patients with SLO (0.87% of total). Mutational analysis of the DHCR7 gene led to the identification of seven distinct mutations, three of which are new (F174S, H301R, and Q98X). The common IVS8-1G > C and T93M variants together with the H301R accounted for 70% of the all SLO alleles in our population. Our findings contribute to the variegate array of pathological changes in the DHCR7 gene among different European populations.
Cardoso
M L
ML
Instituto de Genética Médica Jacinto de Magalhães, Oporto, Portugal.
Balreira
A
A
Martins
E
E
Nunes
L
L
Cabral
A
A
Marques
M
M
Lima
M Reis
MR
Marques
J S
JS
Medeira
A
A
Cordeiro
I
I
Pedro
S
S
Mota
M C
MC
Dionisi-Vici
C
C
Santorelli
F M
FM
Jakobs
C
C
Clayton
P T
PT
Vilarinho
L
L
D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000097:blood / Q000235:genetics*; D011174:Portugal; D019082:Smith-Lemli-Opitz Syndrome / Q000097:blood / Q000235:genetics*
D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase