Smith-Lemli-Opitz syndrome: new mutation with a mild phenotype

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder impacting cholesterol biosynthesis.
• SLOS is caused by mutations in the DHCR7 gene, which encodes 3beta-hydroxysterol Delta(7)-reductase.
• The enzyme's deficiency leads to reduced cholesterol and elevated 7-dehydrocholesterol levels.

Purpose of the Study:

• To investigate the genetic basis of a mild SLOS phenotype in an infant.
• To identify novel mutations in the DHCR7 gene associated with SLOS.
• To correlate genotype with the observed clinical presentation.

Main Methods:

• Clinical evaluation of an infant with suspected SLOS, including assessment of physical anomalies and developmental milestones.
• Biochemical analysis of plasma cholesterol and 7-dehydrocholesterol levels.
• Molecular genetic analysis of the DHCR7 gene to identify mutations.

Main Results:

• The patient presented with mild SLOS symptoms, including feeding difficulties, hypotonia, and minor dysmorphic features.
• Biochemical tests confirmed SLOS with borderline low cholesterol and elevated 7-dehydrocholesterol.
• Molecular analysis revealed compound heterozygosity for a known null mutation and a novel missense mutation (Y280C) in DHCR7.

Conclusions:

• A novel missense mutation in DHCR7 (Y280C) is associated with a mild SLOS phenotype.
• This new mutation likely confers significant residual enzyme activity.
• Genotype-phenotype correlations in SLOS are further elucidated, highlighting the impact of residual enzyme function.