Molecular cytogenetic characterization of a rare recombinant chromosome 22 caused by a maternal intrachromosomal insertion

The formation of recombinant chromosomes in the offspring of inversion and insertion carriers constitutes a significant challenge in clinical genetics due to the high risk of chromosomal abnormalities in children. Here, we present a clinical case. The aim of this study was to characterize the structure and origin of a chromosomal imbalance in a female patient presenting with delayed motor and speech development, craniofacial anomalies, and sensorineural hearing loss through molecular cytogenetic analysis of a recombinant chromosome 22. Chromosomal microarray analysis of the proband, who exhibited psychomotor delay and dysmorphic features, revealed three interstitial duplications: 22q11.21, 22q12.3–q13.1, and 22q13.2. Fluorescence in situ hybridization (FISH), using both commercial and homemade DNA probes, demonstrated that the mother carried a complex intrachromosomal rearrangement comprising an initial paracentric inversion of 22q11.21–q12.3, followed by an interstitial insertion of the 22q11.21 and 22q12.3–q13.1 segments into the nucleolar organizer region at 22p12. Accordingly, the recombinant chromosome identified in the proband resulted from meiotic segregation of the maternal complex intrachromosomal inversion and insertion. These findings highlight the diagnostic value of an integrated cytogenomic approach for the precise delineation of complex chromosomal rearrangements, determination of their origin, and assessment of genetic risk in clinical genetic counseling.