SCIENTIFIC BACKGROUND

DHCR7

Smith-Lemli-Opitz syndrome (SLOS) is characterized by a wide range of symptoms that depend on the severity. They include signs of dysmorphia (microcephaly, "midline defect," microretrognathia, low-set ears, blepharoptosis, postaxial polydactyly), psychomotor retardation, short stature, and malformations such as heart defects and cleft lip and/or palate. Affected boys may also have genital malformations (e.g., hypospadias). The molecular cause is a disturbance of the last step of the cholesterol synthesis pathway, resulting in the accumulation of 7-dehydrocholesterol (and its isomer 8-dehydrocholesterol). Since conventional enzymatic cholesterol determination cannot differentiate cholesterol from 7-dehydrocholesterol, biochemical detection of SLOS is performed by gas chromatography/mass spectrometry. An elevated 7-dehydrocholesterol/cholesterol ratio is indicative of SLOS.

 

The inheritance of SLOS follows an autosomal recessive pattern. The prevalence is 1:10,000 to 1:30,000. Pathogenic variants in the DHCR7 gene, which codes for the enzyme 7-dehydrocholesterol reductase, lead to loss of enzyme activity and thus to failure of the last step in cholesterol synthesis. The most common causative variant (c.964-1G>C) is located in intron 8 of the DHCR7 gene. It can be detected in about 30% of all patients. Types of variants and loci in the gene influence the severity of SLOS. However, a clear genotype-phenotype correlation does not always exist, so that patients with the same variants may be affected to different degrees. Therefore, other factors may influence the phenotype. A 2004 study demonstrated a correlation between maternal ApoE genotype and severity in patients with SLOS.

 

References
Nowaczyk M.J.M. 2013, GeneReviews® [Internet] / Corso et al. 2011, Clin Chem Lab Med 12:2039 / DeBarber et al. 2011, Expert Rev Mol Med 13:e24 / Yu et Patel 2005, Clin Genet 68:383 / Witsch-Baumgartner et al. 2004, J Med Genet 41:577

GENES

DHCR7

ASSOCIATED TESTS

How to order

LATEST ARTICLES

We're thrilled to share the results of Medicover Genetics essay competition for high school students as well as the two winning essays. This competit...

Read more

Cystic fibrosis (CF) is a life-threatening, progressive, inherited condition that causes severe damage to the body, primarily affecting the organs of...

Read more

Down syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21. It affects physical growth, facial features, and cogni...

Read more

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more