Exome sequencing for the differential diagnosis of ciliary chondrodysplasias: Example of a WDR35 mutation case and review of the literature.
Eur J Med Genet
; 60(12): 658-666, 2017 Dec.
Article
in En
| MEDLINE
| ID: mdl-28870638
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone and Bones
/
Ectodermal Dysplasia
/
Ellis-Van Creveld Syndrome
/
Proteins
/
Mutation, Missense
/
Craniosynostoses
/
Ciliopathies
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Eur J Med Genet
Journal subject:
GENETICA MEDICA
Year:
2017
Document type:
Article