ArticleProceedings of the National Academy of Sciences of the United States of America1997
Synpolydactyly phenotypes correlate with size of expansions in HOXD13 polyalanine tract.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 213 citations in OpenAlex.
- The intersection of disorders of sex development and cardiovascular diseases.Biology of sex differences · 2026Review
- Chromosomal localization of PHOX2B during M-phase is disrupted in disease-associated mutants.Development, growth & differentiation · 2025Article
- A novel Hoxd13 mutation causes synpolydactyly and promotes osteoclast differentiation by regulating pSmad5/p65/c-Fos/Rank axis.Cell death & disease · 2023Article
- Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract.Frontiers in genetics · 2023Article
- A Novel Missense Variant ofFrontiers in genetics · 2021Article
- Article
- A Review of the Phenotype of Synpolydactyly Type 1 in Homozygous Patients: Defining the Relatively Long and Medially Deviated Big Toe with/without Cupping of the Forefoot as a Pathognomonic Feature in the Phenotype.BioMed research international · 2020Review
- A heterozygous duplication variant of the HOXD13 gene caused synpolydactyly type 1 with variable expressivity in a Chinese family.BMC medical genetics · 2019Article
- Proteomic analysis reveals that wildtype and alanine-expanded nuclear poly(A)-binding protein exhibit differential interactions in skeletal muscle.The Journal of biological chemistry · 2019Article
- Intrafamilial variability of the triphalangeal thumb phenotype in a Dutch population: Evidence for phenotypic progression over generations?American journal of medical genetics. Part A · 2017Article
- Interpreting short tandem repeat variations in humans using mutational constraint.Nature genetics · 2017Article
- Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import.The Journal of biological chemistry · 2016Article
- Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.Developmental cell · 2015Article
- Functional classification and mutation analysis of a synpolydactyly kindred.Experimental and therapeutic medicine · 2014Article
- Microsatellite interruptions stabilize primate genomes and exist as population-specific single nucleotide polymorphisms within individual human genomes.PLoS genetics · 2014Article
- Mutations in the homeodomain of HOXD13 cause syndactyly type 1-c in two Chinese families.PloS one · 2014Article
- Article
- Structural and functional insights into the heme-binding domain of the human soluble guanylate cyclase α2 subunit and heterodimeric α2β1.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2012Article
- Isolated brachydactyly type E caused by a HOXD13 nonsense mutation: a case report.BMC medical genetics · 2012Article
- The homeobox transcription factor HOXA9 is a regulator of SHOX in U2OS cells and chicken micromass cultures.PloS one · 2012Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Synpolydactyly (SPD) is a dominantly inherited congenital limb malformation. Typical cases have 3/4 finger and 4/5 toe syndactyly, with a duplicated digit in the syndactylous web, but incomplete penetrance and variable expressivity are common. The condition has recently been shown to be caused by expansions of an imperfect trinucleotide repeat sequence encoding a 15-residue polyalanine tract in HOXD13. We have studied 16 new and 4 previously published SPD families, with between 7 and 14 extra residues in the tract, to analyze the molecular basis for the observed variation in phenotype. Although there is no evidence of change in expansion size within families, even over six generations, there is a highly significant increase in the penetrance and severity of phenotype with increasing expansion size, affecting both hands (P = 0.012) and feet (P < 0. 00005). Affected individuals from a family with a 14-alanine expansion, the largest so far reported, all have a strikingly similar and unusually severe limb phenotype, involving the first digits and distal carpals. Affected males from this family also have hypospadias, not previously described in SPD, but consistent with HOXD13 expression in the developing genital tubercle. The remarkable correlation between phenotype and expansion size suggests that expansion of the tract leads to a specific gain of function in the mutant HOXD13 protein, and has interesting implications for the role of polyalanine tracts in the control of transcription.
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