Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata

Shiro Ikegawa, Hirofumi Ohashi, Tsutomu Ogata, Akira Honda, Masato Tsukahara, Toshihide Kubo, Mamori Kimizuka, Masanori Shimode, Tomonobu Hasegawa, Gen Nishimura, Yusuke Nakamura

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


Chondrodysplasia punctata (CDP) is a heterogeneous group of skeletal dysplasias characterized by stippled epiphyses. A subtype of CDP, X-linked dominant chondrodysplasia punctata (CDPX2), known also as Conradi-Hunermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. The cause of CDPX2 was unknown until recent identification of mutations in the gene encoding Δ87 sterol isomerase emopamil-binding protein (EBP). Twelve different EBP mutations have been reported in 14 patients with CDPX2 or unclassified CDP, but with no evidence of correlation between phenotype and nature of the mutation. To characterize additional mutations and investigate possible phenotype-genotype correlation, we sequenced the entire EBP gene in 8 Japanese individuals with CDP; 5 of them presented with a CDPX2 phenotypes. We found EBP mutations in all 5 CDPX2 individuals, but none in non-CDPX2 individuals. Three of these CDPX2 individuals carried novel nonsense mutations in EBP and the other two, separate missense mutations that had been reported also in different ethnic groups. Our results, combined with previous information, suggest all EBP mutations that produce truncated proteins result in typical CDPX2, whereas the phenotypes resulted from missense mutations are not always typical for CDPX2. Patients with nonsense mutations showed abnormal sterol profiles consistent with a defect in Δ8, Δ7 sterol isomerase. X-inactivation patterns of the patients showed no skewing, an observation that supports the assumption that inactivation of the EBP gene occurs at random in affected individuals. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)300-305
Number of pages6
JournalAmerican journal of medical genetics
Issue number4
Publication statusPublished - 2000 Oct 2


  • Chondrodysplasia punctata
  • EBP mutation
  • Skeletal dysplasia
  • Steroid metabolism
  • X inactivation

ASJC Scopus subject areas

  • Genetics(clinical)


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