Reanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant in A Newly Associated Gene for Jeune Syndrome Phenotype.

INTRODUCTION

Ciliopathies with major skeletal involvement embrace a group of heterogeneous disorders caused by pathogenic variants in a group of diverse genes. A narrow thorax with shortening of long bones inspires a clinical entity underlined by dysfunction of primary cilia. Currently, more than 23 genes are listed in the OMIM database corresponding to this clinical entity: WDR19/34/35/60, IFT43/52/80/81/140/172, DYNC2LI1, TTC21B, DYNLT2B, EVC2, EVC, INTU, NEK1, CEP120, DYNC2H1, KIAA0586, SRTD1, KIAA0753, and SRTD12. Recently, individuals with biallelic loss-of-function variants in are shown to demonstrate a phenotype compatible with Jeune syndrome. Experimental evidence has shown that impaired function of compromises cilia-based signaling of Hedgehog pathway as well as Wnt signaling, while cilia morphology remains intact. Hence, is now considered an essential protein in regulation of the skeletogenesis.

CASE PRESENTATION

We presented a female infant born to a consanguineous marriage who was found to have a biallelic p.R474* alteration in in reanalysis of the whole-exome sequencing (WES) data. The patient was exhibiting major clinical features of Jeune syndrome, such as shortened long bones, ribs, and narrow thorax.

DISCUSSION

Our reanalysis of WES data revealed a likely pathogenic biallelic variant in the which is probably responsible for the Jeune syndrome phenotype in the patient. Hence, our report supports the recently discovered association of loss-of-function variants with Jeune syndrome phenotype and emphasizes the significance of reanalysis of WES data, notably in patients with phenotypes suggestive of a such discernible Mendelian disorder.