Abstract
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 Δ8,Δ7 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 language | English |
|---|---|
| Pages (from-to) | 300-305 |
| Number of pages | 6 |
| Journal | American Journal of Medical Genetics |
| Volume | 94 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2000 Oct 2 |
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Keywords
- Chondrodysplasia punctata
- EBP mutation
- Skeletal dysplasia
- Steroid metabolism
- X inactivation
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata. / Ikegawa, Shiro; Ohashi, Hirofumi; Ogata, Tsutomu; Honda, Akira; Tsukahara, Masato; Kubo, Toshihide; Kimizuka, Mamori; Shimode, Masanori; Hasegawa, Tomonobu; Nishimura, Gen; Nakamura, Yusuke.
In: American Journal of Medical Genetics, Vol. 94, No. 4, 02.10.2000, p. 300-305.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata
AU - Ikegawa, Shiro
AU - Ohashi, Hirofumi
AU - Ogata, Tsutomu
AU - Honda, Akira
AU - Tsukahara, Masato
AU - Kubo, Toshihide
AU - Kimizuka, Mamori
AU - Shimode, Masanori
AU - Hasegawa, Tomonobu
AU - Nishimura, Gen
AU - Nakamura, Yusuke
PY - 2000/10/2
Y1 - 2000/10/2
N2 - 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 Δ8,Δ7 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.
AB - 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 Δ8,Δ7 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.
KW - Chondrodysplasia punctata
KW - EBP mutation
KW - Skeletal dysplasia
KW - Steroid metabolism
KW - X inactivation
UR - http://www.scopus.com/inward/record.url?scp=0034597344&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034597344&partnerID=8YFLogxK
U2 - 10.1002/1096-8628(20001002)94:4<300::AID-AJMG7>3.0.CO;2-3
DO - 10.1002/1096-8628(20001002)94:4<300::AID-AJMG7>3.0.CO;2-3
M3 - Article
VL - 94
SP - 300
EP - 305
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 4
ER -