Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

Autor:	Balasubramanian M; Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK., Lord H; Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, The Churchill Hospital, Oxford, UK., Levesque S; Department of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada., Guturu H; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Thuriot F; Department of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada., Sillon G; Department of Medical Genetics, McGill University Health Center, Montreal, Quebec, Canada., Wenger AM; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Sureka DL; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Lester T; Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, The Churchill Hospital, Oxford, UK., Johnson DS; Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK., Bowen J; Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK., Calhoun AR; Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA., Viskochil DH; School of Medicine, Pediatric Genetics, Salt Lake City, Utah, USA., Bejerano G; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.; Department of Computer Science, Stanford University, Stanford, California, USA.; Department of Developmental Biology, Stanford University, Stanford, California, USA., Bernstein JA; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA., Chitayat D; The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada.; Division of Clinical Genetics and Metabolism, Department of Pediatrics, The Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2017 Mar; Vol. 54 (3), pp. 157-165. Date of Electronic Publication: 2016 Oct 13.
DOI:	10.1136/jmedgenet-2016-104143
Abstrakt:	Background: In 1993, Chitayat et al. , 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. Objectives: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. Methods: 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. Results: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF 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 ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. Discussion: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. Conclusions: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF . (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)
Databáze:	MEDLINE
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