Synpolydactyly 1 (HOXD13)
| Dred_ID | RD00018 |
| OMIM ID | 186000 |
| Disease name | Synpolydactyly 1 |
| Alternative names | SPD1 SPD2 |
| Category | Genetic diseases, Bone diseases, Fetal diseases, Rare diseases |
| Phenotype | OMIM: Synpolydactyly (SPD), or syndactyly type II, is defined as a connection between the middle and ring fingers and fourth and fifth toes, variably associated with postaxial polydactyly in the same digits. Minor local anomalies and various metacarpal or metatarsal abnormalities may be present (summary by Merlob and Grunebaum, 1986). In some families with SPD, the foot anomalies are characterized by preaxial as well as postaxial polydactyly, and appear to be fully penetrant. The more severe features of classic SPD, involving 3/4 synpolydactyly in the hands and 4/5 synpolydactyly in the feet, also occur, but at reduced penetrance. This foot phenotype is not seen in patients with classic SPD due to HOXD13 polyalanine tract expansions (Goodman et al., 1998). Malik (2012) reviewed the syndactylies, noting that the extreme phenotypic heterogeneity observed in SPD families consists of approximately 18 clinical variants that can be 'lumped' into 3 categories: typical SPD features, minor variants, and unusual phenotypes. |
| Miscellaneouse | OMIM: marked intrafamilial variability, with homozygotes exhibiting a more severe phenotype and heterozygotes showing milder features |
| Prevalence | N/A [source: MalaCards] |
| Inheritance | Autosomal dominant |
| Anticipation | N/A |
| Evidence | Strong |
| Gene symbol | HOXD13 |
| Alias symbols | BDE; SPD; BDSD; HOX4I |
| Gene name | homeobox D13 |
| Gene map locus | 2q31.1; chr2:176,087,487-176,095,944(+) |
| Ensembl Gene ID | ENSG00000128714 |
| Gene expression and Gene Ontology | BioGPS |
| Protein expression | Human Protein Atlas |
| Gene sequence | Sequence |
| Variation | ClinVar, dbSNP | Gene conservation | Gene Conservation from UCSC Genome Browser |
| Gene Description | This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. Mutations in this particular gene cause synpolydactyly. [provided by RefSeq, Jul 2008] |
| Repeat unit | GCG |
| Normal repeat copies | 15 |
| Pathogenic repeat copies | ≥22 |
| Gene | HOXD13 |
| Repeat location | CDS |
| Chromosome locus | chr2:176093059-176093100 (+) |
| Repeat conservation | Repeat Conservation from UCSC Genome Browser |
| Toxic cause | Protein |
| Possible toxicity | The HOXD13 gene, encoding a polypeptide of 335 amino acids, contains 2 exons and has high homology to the chicken HOXD13 gene. The protein encoding HOXD13 has 2 Ser stretches and 1 Ala stretch of 15 amino acid residues.HOXD13 mutations leading to typical or atypical SPD include polyalanine expansion and contraction (deletions) nonsense mutation and missense mutation |
| Pathway annotation | Reactome, KEGG |
| PMID | 8817328 |
| Authors | Akarsu AN, Stoilov I, Yilmaz E, Sayli BS, Sarfarazi M |
| Title | Genomic structure of HOXD13 gene: a nine polyalanine duplication causes synpolydactyly in two unrelated families |
| Journal | Hum Mol Genet. 5(7):945-52 |
| Year | 1996 |