Format

Send to

Choose Destination
J Med Genet. 2017 Mar;54(3):157-165. doi: 10.1136/jmedgenet-2016-104143. Epub 2016 Oct 13.

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

Author information

1
Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, UK.
2
Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, The Churchill Hospital, Oxford, UK.
3
Department of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada.
4
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
5
Department of Medical Genetics, McGill University Health Center, Montreal, Quebec, Canada.
6
Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.
7
School of Medicine, Pediatric Genetics, Salt Lake City, Utah, USA.
8
Department of Computer Science, Stanford University, Stanford, California, USA.
9
Department of Developmental Biology, Stanford University, Stanford, California, USA.
10
The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada.
11
Division of Clinical Genetics and Metabolism, Department of Pediatrics, The Hospital for Sick Children; University of Toronto, Toronto, Ontario, Canada.

Abstract

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.

KEYWORDS:

Bronchomalacia; Chitayat syndrome; Craniosynostosis; ERF; Hyperphalangism

PMID:
27738187
DOI:
10.1136/jmedgenet-2016-104143
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire Icon for White Rose Research Online
Loading ...
Support Center