Mutations in the gene encoding 3β-hydroxysteroid-Δ87-isomerase cause X-linked dominant Conradi-Hunermann syndrome

Nancy Braverman, Paul Lin, Fabian F. Moebius, Cassandra Obie, Ann Moser, Hartmut Glossmann, William R. Wilcox, David L. Rimoin, Moyra Smith, Lisa Kratz, Richard I. Kelley, David Valle

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221 Scopus citations


X-linked dominant Conradi-Hunermann syndrome (CDPX2; MIM 302960) is one of a group of disorders with aberrant punctate calcification in cartilage, or chondrodysplasia punctata (CDP). This is most prominent around the vertebral column, pelvis and long bones in CPDX2. Additionally, CDPX2 patients may have asymmetric rhizomesomelia, sectorial cataracts, patchy alopecia, ichthyosis and atrophoderma. The phenotype in CDPX2 females ranges from stillborn to mildly affected individuals identified in adulthood. CDPX2 is presumed lethal in males, although a few affected males have been reported. We found increased 8(9)-cholestenol and 8-dehydrocholesterol in tissue samples from seven female probands with CDPX2 (ref. 4). This pattern of accumulated cholesterol intermediates suggested a deficiency of 3β-hydroxysteroid- Δ87-isomerase (sterol-Δ8-isomerase), which catalyses an intermediate step in the conversion of lanosterol to cholesterol. A candidate gene encoding a sterol-Δ8-isomerase (EBP) has been identified and mapped to Xp11.22-p11.23 (refs 5,6). Using SSCP analysis and sequencing of genomic DNA, we found EBP mutations in all probands. We confirmed the functional significance of two missense alleles by expressing them in a sterol-Δ8- isomerase-deficient yeast strain. Our results indicate that defects in sterol-Δ8-isomerase cause CDPX2 and suggest a role for sterols in bone development.

Original languageEnglish (US)
Pages (from-to)291-294
Number of pages4
JournalNature genetics
Issue number3
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Genetics


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