EBP:c.440G>A (p.Arg147His) AND Chondrodysplasia punctata 2 X-linked dominant

Clinical significance:Pathogenic (Last evaluated: Apr 4, 2013)

Review status:

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000012247.10

Allele description [Variation Report for EBP:c.440G>A (p.Arg147His)]

Gene:
EBP:emopamil binding protein (sterol isomerase) [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.23
Genomic location:
Preferred name:
EBP:c.440G>A (p.Arg147His)
HGVS:
  • NC_000023.11:g.48527256G>A
  • NG_007452.1:g.10481G>A
  • NM_006579.2:c.440G>A
  • NP_006570.1:p.Arg147His
  • NC_000023.10:g.48385644G>A
Protein change:
R147H; ARG147HIS
Links:
OMIM: 300205.0012; dbSNP: 28935174
NCBI 1000 Genomes Browser:
rs28935174
Molecular consequence:
  • NM_006579.2:c.440G>A: missense variant [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Chondrodysplasia punctata 2 X-linked dominant (CDPX2)
Synonyms:
CONRADI-HUNERMANN-HAPPLE SYNDROME; Happle syndrome; Conrad Hunermann Happle syndrome; See all synonyms [MedGen]
Identifiers:
MedGen: C0282102; OMIM: 302960; Orphanet: 35173
Age of onset:
Neonatal/infancy
Prevalence:
  • 1-9 / 1 000 000 Orphanet: 35173
  • Based on rates of biochemical diagnosis of CDPX2 compared to Smith-Lemli-Opitz syndrome (incidence of 1 in 75-100,000 births) in one laboratory, the recognized incidence of CDPX2 is no more than one fifth the rate for Smith-Lemli-Opitz syndrome, or no greater than approximately one in 400,000 births. This number may be an underestimate because of individuals with milder features who may not be accurately diagnosed.

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000032481OMIMPathogenic
(Apr 4, 2013)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

The Conradi-Hünermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism.

Has C, Bruckner-Tuderman L, Müller D, Floeth M, Folkers E, Donnai D, Traupe H.

Hum Mol Genet. 2000 Aug 12;9(13):1951-5.

PubMed [citation]
PMID:
10942423

Skewed X-chromosome inactivation causes intra-familial phenotypic variation of an EBP mutation in a family with X-linked dominant chondrodysplasia punctata.

Shirahama S, Miyahara A, Kitoh H, Honda A, Kawase A, Yamada K, Mabuchi A, Kura H, Yokoyama Y, Tsutsumi M, Ikeda T, Tanaka N, Nishimura G, Ohashi H, Ikegawa S.

Hum Genet. 2003 Jan;112(1):78-83. Epub 2002 Oct 24.

PubMed [citation]
PMID:
12483303
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000032481.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

Has et al. (2000) described a family in which 2 children with CDPX2 (302960) had an arg147-to-his (R147H) mutation of the EBP gene but showed differing severity of the disease. Shirahama et al. (2003) described a patient with the same mutation, caused by a 440G-A transition in exon 4, which was also found in her clinically unaffected mother. Expression analysis demonstrated that the mutant allele was predominantly expressed in the patient, while both alleles were expressed in her mother. Methylation analysis revealed that the wildtype allele was predominantly inactivated in the patient, while the mutated allele was predominantly inactivated in her mother. Thus, differences in expression of the mutated allele caused by skewed X-chromosome inactivation produced the diverse phenotypes within this family. Shirahama et al. (2003) noted that anticipation was a striking clinical feature of CDPX2 in the studies of Sutphen et al. (1995) and Traupe et al. (1992) and suggested that skewed methylation may have a role in this phenomenon.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 27, 2014

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