De novo 22q11.2 deletions and auricular findings in two Chinese patients with microtia

Congenital microtia is a common craniofacial malformation resulting from both environmental and genetic factors. Recurrent chromosomal imbalances were observed in patients with microtia. The 22q11.2 deletion is one of the most common microdeletions in human beings. The cell division cycle 45 gene (CDC45) embedded in the proximal 22q11.2 deleted region is involved in craniofacial development. However, only a few studies have focused on the 22q11.2 deletion as genetic etiology in microtia patients and studied its associated external ear deformity characteristics in detail.

In this research, a total of 65 patients from north China with sporadic microtia were studied. Copy number variations of CDC45 were screened using AccuCopy assay. The 22q11.2 deletion harboring CDC45 was identified by whole-genome sequencing and targeted next-generation sequencing. A parental test was carried out to determine the origin of the deletion.

CDC45 copy number loss was identified in two patients with microtia. A set of qPCR assays demonstrated two patients carried a typical proximal 22q11.2 deletion between the low-copy repeats on chromosome 22q11.2 (LCR22A and LCR22D), encompassing CDC45. The 22q11.2 deletions were de novo in each patient. In-depth auricular phenotype assessment showed these two patients have a distinct concha-type ear malformation while other microtia patients have lobule-type microtia among the 65 microtia patient cohort in this study.

Here we present two additional Chinese microtia patients with de novo 22q11.2 proximal deletion harboring CDC45 and further report these patients' distinct ear malformation.