Thus, the human CDPX2 gene probably maps within Xq27-Xq28 and not within Xp22.3-Xpter, where deletions associated with X-linked recessive chondrodysplasia punctata (CDPX) have been noted.
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.
Mutations of the gene coding for emopamil binding protein (EBP) can lead to deficient activity of 3-β-hydroxysteroid Δ(8), Δ(7) isomerase and are most commonly identified in. association with the X-linked dominant (male lethal) chondrodysplasia punctata (CDPX2), also known as Conradi-Hunermann syndrome.
Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes.
Conradi-Hünermann-Happle syndrome, also known as chondrodysplasia punctata type 2 (CDPX2), is an X-linked dominant disorder characterized by skin defects, skeletal and ocular abnormalities.
Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata (CP) caused by mutations in one gene of the distal pathway of cholesterol biosynthesis.
The X-linked dominant Conradi-Hünermann-Happle (CDPX2, MIM 302960) syndrome belongs to the rare, heterogeneous group of diseases called chondrodysplasia punctata.
First, the absence of stippled epiphyses on radiograms should not be considered an exclusion criteria for ARSE mutation screening in patients with other features of the disease, especially after the neonatal period.
These include the gene encoding arylsulfatase E, which is involved in X-linked recessive chondrodysplasia punctata, a disorder of cartilage and bone development.
The ARSE gene was also deleted on the dic (X;Y) chromosome but chondrodysplasia punctata was not expressed, as CDP is recessive and ARSE escapes inactivation on the normal X chromosome.
The clinical description of patients with CDPX due to known mutation of the ARSE is of interest for the precise delineation of the clinical spectrum of the disease.
Thus, screening for arylsulfatase E mutation is mandatory for an accurate diagnosis and can lead to better delineation among CP etiologies associated with a Binder phenotype.
Several of these genes are associated with known disorders, like KAL1 (Kallmann syndrome), steroid sulfatase (STS) (X-linked ichtyosis), and arylsulfatase E (ARSE) (chondrodysplasia punctata).
Interestingly, this patient is the first case with a proven loss of the ARSE gene without chondrodysplasia punctata, assuming that chondrodysplasia punctata is not an obligatory sign of ARSE gene loss.
Clinical features suggestive of Keutel syndrome were also observed in one additional unrelated patient who was later found to have a deletion of arylsulfatase E, consistent with a diagnosis of X-linked recessive chondrodysplasia punctata.