Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature

Dinu Antony, Narayanan Nampoory, Chiara Bacchelli, Motasem  Melhem, Kaman Wu, Chela T. James, Philip L. Beales, Mike Hubank, Daisy Thomas, Anant Mashankar, Kazem Behbehani, Miriam Schmidts, Osama Alsmadi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Exome sequencing is becoming widely popular and affordable, making it one of the most desirable methods for the identification of rare genetic variants for clinical diagnosis. Here, we report the clinical application of whole exome sequencing for the ultimate diagnosis of a ciliary chondrodysplasia case presented with an initial clinical diagnosis of Asphyxiating Thoracic Dystrophy (ATD, Jeune Syndrome). We have identified a novel homozygous missense mutation in WDR35 (c.206G > A), a gene previously associated with Sensenbrenner Syndrome, Ellis-van Creveld syndrome and Short-rib polydactyly syndrome type V. The genetic findings in this family led to the re-evaluation of the initial diagnosis and a differential diagnosis of Sensenbrenner Syndrome was made after cautious re-examination of the patient. Cell culture studies revealed normal subcellular localization of the mutant WDR35 protein in comparison to wildtype protein, pointing towards impaired protein-protein interaction and/or altered cell signaling pathways as a consequence of the mutated allele. This research study highlights the importance of including pathogenic variant identification in the diagnosis pipeline of ciliary chondrodysplasias, especially for clinically not fully defined phenotypes.

Original languageEnglish
Pages (from-to)658-666
Number of pages9
JournalEuropean Journal of Medical Genetics
Volume60
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • Ciliary chondrodysplasias
  • Exome sequencing

Fingerprint Dive into the research topics of 'Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature'. Together they form a unique fingerprint.

  • Cite this

    Antony, D., Nampoory, N., Bacchelli, C., Melhem, M., Wu, K., James, C. T., Beales, P. L., Hubank, M., Thomas, D., Mashankar, A., Behbehani, K., Schmidts, M., & Alsmadi, O. (2017). Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature. European Journal of Medical Genetics, 60(12), 658-666. https://doi.org/10.1016/j.ejmg.2017.08.019