ORPHA: 95706; DO: 10892;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| Xq28 | Hypospadias 2, X-linked | 300758 | X-linked recessive | 3 | MAMLD1 | 300120 |
A number sign (#) is used with this entry because X-linked isolated hypospadias-2 (HYSP2) can be caused by mutation in the MAMLD1 gene (300120) on chromosome Xq28.
For a phenotypic description and a discussion of genetic heterogeneity of hypospadias, see 300633.
Hypospadias is a common malformation in which the urethra opens on the ventral side of the penis (Fukami et al., 2006).
Fukami et al. (2006) performed direct sequencing of the coding exons 3-6 of the CXORF6 (MAMLD1) gene and their flanking splice sites in 166 individuals with various types of 46,XY disorders of sex development. They identified 3 nonsense mutations (300120.0001-300120.0003) in 4 Japanese individuals with penoscrotal hypospadias as the conspicuous phenotype. The mutations were predicted to cause nonsense-mediated mRNA decay because of their positions. Consistent with this, RT-PCR for leukocytes indicated markedly reduced transcripts. All affected individuals had seemingly normal pituitary-gonadal serum hormone levels.
Fukami, M., Wada, Y., Miyabayashi, K., Nishino, I., Hasegawa, T., Nordenskjold, A., Camerino, G., Kretz, C., Buj-Bello, A., Laporte, J., Yamada, G., Morohashi, K., Ogata, T. CXorf6 is a causative gene for hypospadias. Nature Genet. 38: 1369-1371, 2006. Note: Erratum: Nature Genet. 39: 131 only, 2007. [PubMed: 17086185] [Full Text: https://doi.org/10.1038/ng1900]