ArticleGenetics in medicine : official journal of the American College of Medical Genetics2018
A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 27 citations in OpenAlex.
- Inherited non-syndromic polydactyly in a Berber and Arabian-Berber horse family.Equine veterinary journal · 2025Article
- Genetic analysis of preaxial polydactyly: identification of novel variants and the role of ZRS duplications in a Chinese cohort of 102 cases.Human genetics · 2024Article
- Chromatin remodeller Chd7 is developmentally regulated in the neural crest by tissue-specific transcription factors.PLoS biology · 2024Article
- Evolutionary genetics of flipper forelimb and hindlimb loss from limb development-related genes in cetaceans.BMC genomics · 2022Article
- The pZRS non-coding regulatory mutation resulting in triphalangeal thumb-polysyndactyly syndrome changes the pattern of local interactions.Molecular genetics and genomics : MGG · 2022Article
- Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis.Orphanet journal of rare diseases · 2022Review
- ZPA Regulatory Sequence Variants in Chinese Patients With Preaxial Polydactyly: Genetic and Clinical Characteristics.Frontiers in pediatrics · 2022Article
- Prenatal diagnosis of triphalangeal thumb-polysyndactyly syndrome by ultrasonography combined with genetic testing: A case report.World journal of clinical cases · 2021Article
- Complex radial polydactyly in a Chinese family: inclusion of triphalangism, triplication, and syndactyly.Annals of translational medicine · 2021Article
- A self-amplifying loop of YAP and SHH drives formation and expansion of heterotopic ossification.Science translational medicine · 2021Article
- Identification of the genetic basis of sporadic polydactyly in China by targeted sequencing.Computational and structural biotechnology journal · 2021Article
- GLIS Family Zinc Finger 1 was First Linked With Preaxial Polydactyly I in Humans by Stepwise Genetic Analysis.Frontiers in cell and developmental biology · 2021Article
- A 300-kb microduplication of 7q36.3 in a patient with triphalangeal thumb-polysyndactyly syndrome combined with congenital heart disease and optic disc coloboma: a case report.BMC medical genomics · 2020Article
- Expression of Fibroblast Growth Factor 4 in a Rat Model of Polydactyly of the Thumb Induced by Cytarabine.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- A multidisciplinary review of triphalangeal thumb.The Journal of hand surgery, European volume · 2019Review
- Beyond the Exome: The Non-coding Genome and Enhancers in Neurodevelopmental Disorders and Malformations of Cortical Development.Frontiers in cellular neuroscience · 2019Article
- A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis.BioMed research international · 2019Review
- Clinical Genetics of Polydactyly: An Updated Review.Frontiers in genetics · 2018Article
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe zone of polarizing activity regulatory sequence (ZRS) is an enhancer that regulates sonic hedgehog during embryonic limb development. Recently, mutations in a noncoding evolutionary conserved sequence 500 bp upstream of the ZRS, termed the pre-ZRS (pZRS), have been associated with polydactyly in dogs and humans. Here, we report the first case of triphalangeal thumb-polysyndactyly syndrome (TPT-PS) to be associated with mutations in this region and show via mouse enhancer assays how this mutation leads to ectopic expression throughout the developing limb bud.
methodsWe used linkage analysis, whole-exome sequencing, Sanger sequencing, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, single-nucleotide polymorphism array, and a mouse transgenic enhancer assay.
resultsTen members of a TPT-PS family were included in this study. The mutation was linked to chromosome 7q36 (LOD score 3.0). No aberrations in the ZRS could be identified. A point mutation in the pZRS (chr7:156585476G>C; GRCh37/hg19) was detected in all affected family members. Functional characterization using a mouse transgenic enhancer essay showed extended ectopic expression dispersed throughout the entire limb bud (E11.5).
conclusionOur work describes the first mutation in the pZRS to be associated with TPT-PS and provides functional evidence that this mutation leads to ectopic expression of this enhancer within the developing limb.
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