Clinical and Genetic Analysis of Pediatric Neurodevelopmental Disorders With Complex Chromosomal Rearrangements in Two Cases.

OBJECTIVE

Our study investigates the impact of junction breakpoints of complex chromosomal rearrangements (CCRs) on developmental delay and intermittent epilepsy in children, aiming to elucidate the underlying genetic mechanisms.

METHODS

We reported a patient with developmental delay in family 1, and we reported a patient with intermittent epileptic seizures in family 2. Karyotype analysis was used to detect chromosomal abnormalities. Whole exome sequencing (WES) and/or whole genome sequencing (WGS) can further assist in identifying the genetic etiology.

RESULTS

Our findings revealed a central inversion rearrangement on chromosome 3 affecting the Roundabout Guidance Receptor 1 (ROBO1), DnaJ Heat Shock Protein Family Member C13 (DNAJC13), and Acyl-CoA Dehydrogenase Family Member 11 (ACAD11) genes in patient 1, suggesting its potential pathogenic role in developmental delays. In another patient, we identified a complex rearrangement involving chromosome 1, coupled with a heterozygous mutation in KCNA2 NM_004974.4:c.347A>C (p.Tyr116Ser), indicating a strong association with intermittent seizures.

CONCLUSIONS

Combining chromosome karyotype analysis with WES and/or WGS can accurately locate chromosomal breakpoints and provide more accurate genetic information. It is an important approach for integrated diagnosis.