Journal article
Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene
Journal of medical genetics, Vol.54(3), pp.157-165
03/2017
DOI: 10.1136/jmedgenet-2016-104143
PMID: 27738187
Abstract
In 1993, Chitayat
, reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise.
To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism.
Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5.
A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in
was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent
c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome.
variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis.
We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in
.
Details
- Title: Subtitle
- Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene
- Creators
- M Balasubramanian - Sheffield Children's NHS Foundation TrustH Lord - Churchill HospitalS Levesque - Centre Hospitalier Universitaire de SherbrookeH Guturu - Stanford UniversityF Thuriot - Centre Hospitalier Universitaire de SherbrookeG Sillon - McGill University Health CentreA M Wenger - Stanford UniversityD L Sureka - Stanford UniversityT Lester - Churchill HospitalD S Johnson - Sheffield Children's NHS Foundation TrustJ Bowen - Sheffield Children's NHS Foundation TrustA R Calhoun - University of MinnesotaD H Viskochil - University of UtahG Bejerano - Stanford UniversityJ A Bernstein - Stanford UniversityD Chitayat - University of TorontoDDD Study
- Resource Type
- Journal article
- Publication Details
- Journal of medical genetics, Vol.54(3), pp.157-165
- DOI
- 10.1136/jmedgenet-2016-104143
- PMID
- 27738187
- NLM abbreviation
- J Med Genet
- ISSN
- 0022-2593
- eISSN
- 1468-6244
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984353800502771
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