Smith-Lemli-Opitz syndrome – detection of the 3 most common mutations in the DHCR7 gene (p.Trp151Ter, p.Val326Leu and c.964-1G>C)

Test covered by the reimbursement:
YES
Clinical expertise code:
208
Test without reimbursement:
YES
Gender:
Woman/Man
Material:
Peripheral blood, Buccal swab …
Turnover time:
3 weeks
STATIM:
1 week

Material:

Peripheral blood | 1x 3 ml of whole blood in K3 EDTA tube
Storage after examination: week after the report is issued 2 – 8°C
Buccal swab | 2x swab stick for buccal swab collection
Storage after examination: week after the report is issued 2 – 8°C
Isolated DNA from blood | 10–100 ng/μL of isolated DNA from blood in a PCR tube of at least 15 μL.
Storage after examination: stored in a DNA archive without restriction 15°C
Chorionic villi | Chorionic villi, min. 30 mg tissue in a microtube (Eppendorf type)
Storage after examination: week after the report is issued 2 – 8°C
Amniotic fluid | 3x 10 ml of amniotic fluid in a tube
Storage after examination: week after the report is issued 2 – 8°C
Cord blood | 2–3 ml of cord blood in EDTA
Storage after examination: week after the report is issued 2 – 8°C
Conception product | Foetal tissue in saline
Storage after examination: 1 aliquot is stored -25°C
Cultured cells | 1.5 ml of cultured cells in a microtube (Eppendorf type)
Storage after examination: 180 days 2 – 8°C
Isolated DNA from cordocentesis | 30–100 ng/μL of isolated DNA from cordocentesis in a microtube (Eppendorf type)
Storage after examination: stored in a DNA archive without restriction 15°C
DNA isolated from the product of conception | 50–100 ng/μL in microtube (Eppendorf type)
Storage after examination: stored in a DNA archive without restriction 15°C
Isolated DNA from amniotic fluid | 30–100 ng/μL of isolated DNA from amniocentesis in a microtube (Eppendorf type)
Storage after examination: stored in a DNA archive without restriction 15°C

Quick test description:

Screening of the 3 most common DHCR7 gene mutations: c.452G>A (p.Trp151Ter), c.976G>T (p.Val326Leu), c.964-1G>C (IVS8-1G>C) using Sanger sequencing, which represent about 81% of all mutations in patients with SLOS (Smith-Lemli-Opitz syndrome, OMIM 270400).

Test details:

The DHCR7 gene encodes the enzyme 7-dehydrocholesterol reductase. This enzyme is responsible for the final step in cholesterol production. Mutations in the DHCR7 gene therefore lead to decreased cholesterol and elevated cholesterol precursors leading to Smith–Lemli–Opitz syndrome (SLOS). The accumulation of this cholesterol precursor is embryotoxic and can lead to intrauterine foetal death. The spectrum of malformations in SLOS is quite diverse, e.g. microcephaly, cleft palate, 2/3 finger syndactyly, polydactyly, facial malformations, heart and kidney anomalies, ambiguously differentiated genitalia in boys. Clinical manifestations are highly variable from moderate dysmorphism with mild mental retardation (SLO I) to intrauterine death or death at an early age of the foetus with SLO syndrome (SLO II). SLOS with fully manifested symptoms is estimated to be the cause of some spontaneous abortions. It is the only disease that is treated by administering cholesterol. Sanger sequencing is used to detect the 3 most common mutations in the DHCR7 gene: c.452G>A (p.Trp151Ter), c.976G>T (p.Val326Leu) and c.964-1G>C (IVS8-1G>C). 

Indication

  • positive TT/integrated test, or increased NT in 1st trimester
  • abnormal ultrasound finding in week 20 suspected of SLOS (genitals, heart defect)
  • disabled child suspected of SLOS. 

Procedure for SLOS testing as indicated: 

  1. positive TT/integrated test, or increased NT in 1st trimester: 
    • invasive PND – SLOS testing is performed at our department (screening for the 3 most common mutations c.452G>A (p.Trp151Ter) , c.976G>T (p.Val326Leu) and c.964-1G>C (IVS8-1G>C)), in case of detection of one mutation from screening, isolated DNA is sent to a specialised workplace (University Hospital Brno) to sequence the coding region of the DHCR7 gene. 
  2. Abnormal ultrasound finding at week 20 suspected of SLOS (genitals, heart defect): 
    • invasive PND – isolated DNA is sent from our laboratory to a specialised workplace (University Hospital Brno) to sequence the coding region of the DHCR7 gene
  3. Abnormal ultrasound finding at week 20 suspected of SLOS (genitals, heart defect): 
    • invasive PND – isolated DNA is sent from our laboratory to a specialised workplace (University Hospital Brno) to sequence the coding region of the DHCR7 gene.
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