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A patient with Smith–Lemli–Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement

  • Gabriella P. Szabó
  • Anna V. Oláh
  • Libor Kozak
  • Erzsébet Balogh
  • Andrea Nagy
  • Ivona Blahakova
  • Éva Oláh
Short Report

Abstract

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.

Conclusion

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.

Keywords

Smith–Lemli–Opitz syndrome Simvastatin Cholesterol substitution Novel mutation p.G366V 

Notes

Acknowledgement

We thank to the patient’s parents for their consent. Financial support was not obtained.

References

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Gabriella P. Szabó
    • 1
  • Anna V. Oláh
    • 2
  • Libor Kozak
    • 3
  • Erzsébet Balogh
    • 1
  • Andrea Nagy
    • 1
  • Ivona Blahakova
    • 3
  • Éva Oláh
    • 1
  1. 1.Pediatrics Department, Medical and Health Science CenterDebrecen UniversityDebrecenHungary
  2. 2.Department of Clinical Biochemistry & Molecular Pathology, Medical and Health Science CenterDebrecen UniversityDebrecenHungary
  3. 3.Center of Molecular Biology and Gene TherapyUniversity Hospital BrnoBrnoCzech Republic

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