Variants in CEP135 Cause Congenital Microcephaly and Primary Ciliary Dyskinesia.

CEP135

Bi-allelic CEP135 variants (loss of function or splicing defect); fewer full-length axonemes and bulbous distal ciliary tips

The authors describe three children from two families with congenital primary microcephaly and chronic respiratory disease consistent with primary ciliary dyskinesia (PCD), carrying autosomal recessive CEP135 variants identified by exome sequencing. All had chronic suppurative respiratory symptoms, recurrent otitis media and bronchiectasis, with low nasal nitric oxide. One child carried pathogenic compound heterozygous loss-of-function variants, the other two homozygous variants of uncertain significance, for which transcript analysis supported a disease-causing splicing defect. Cultured nasal epithelial cells showed overall normal ciliary ultrastructure but fewer full-length axonemes, a grossly abnormal beat pattern and bulbous distal tips.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

CEP135, already known in primary microcephaly, here gains a motile ciliopathy dimension: in congenital microcephaly with chronic respiratory disease, PCD should be investigated. The data rest on three children from two families, two of whom carry variants of uncertain significance supported by splicing evidence, which calls for replication. Bulbous ciliary tips, proposed as an electron microscopy marker, still need validation in other ciliopathies.

Analysis by Dr Thibaut Benquey