Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts

Diagnosis of a biochemically atypical case of the syndrome

Akira Honda, G. Stephen Tint, Gerald Salen, Richard I. Kelley, Megumi Honda, Ashok K. Batta, Thomas S. Chen, Sarah Shefer

Research output: Contribution to journalArticle

Abstract

The Smith-Lemli-Opitz syndrome is a common birth defect syndrome caused by a deficiency of 7-dehydrocholesterol Δ7-reductase, an essential enzyme in the biosynthesis of cholesterol. The syndrome can usually be diagnosed easily from the plasma markers of markedly elevated 7-dehydrocholesterol and reduced cholesterol concentrations. However, atypical cases with normal plasma levels of cholesterol with only moderately elevated 7- dehydrocholesterol have been reported. To establish a sensitive method for the biochemical diagnosis of the atypical cases of the syndrome, we measured sterol concentrations of cultured skin fibroblasts. 7-Dehydrocholesterol concentrations in patients' fibroblasts grown in the presence of 10% fetal bovine serum were significantly higher than those in controls and parents (P <0.0005), but they were not elevated proportionately as much as in plasma. To re-produce the accumulation of 7-dehydrocholesterol, the cells were exposed to delipidated medium to induce sterol biosynthesis. After 4 weeks, 7-dehydrocholesterol concentrations in patients' fibroblasts increased from 2.8 ± 0.3% to 34 ± 3% of total sterols (cholesterol + 7-dehydrocholesterol + 8-dehydrocholesterol). The increase was also observed in fibroblasts from an atypical patient who has a normal plasma cholesterol level and a 7- dehydrocholesterol concentration of only 0.15 mg/dl. In contrast, cells from parents and controls accumulated very little 7-dehydrocholesterol (

Original languageEnglish (US)
Pages (from-to)282-287
Number of pages6
JournalAmerican Journal of Medical Genetics
Volume68
Issue number3
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

Smith-Lemli-Opitz Syndrome
Sterols
Fibroblasts
Skin
Cholesterol
Parents
7-dehydrocholesterol

Keywords

  • 7-dehydrocholesterol
  • 8- dehydrocholesterol
  • skin fibroblast
  • Smith-Lemli-Opitz syndrome

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts : Diagnosis of a biochemically atypical case of the syndrome. / Honda, Akira; Stephen Tint, G.; Salen, Gerald; Kelley, Richard I.; Honda, Megumi; Batta, Ashok K.; Chen, Thomas S.; Shefer, Sarah.

In: American Journal of Medical Genetics, Vol. 68, No. 3, 1997, p. 282-287.

Research output: Contribution to journalArticle

Honda, Akira ; Stephen Tint, G. ; Salen, Gerald ; Kelley, Richard I. ; Honda, Megumi ; Batta, Ashok K. ; Chen, Thomas S. ; Shefer, Sarah. / Sterol concentrations in cultured Smith-Lemli-Opitz syndrome skin fibroblasts : Diagnosis of a biochemically atypical case of the syndrome. In: American Journal of Medical Genetics. 1997 ; Vol. 68, No. 3. pp. 282-287.
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