A rare case of uniparental disomy 9 concomitant with low-level mosaicism

Uniparental disomy of chromosome 9, in combination with low-level mosaicism for chromosome 9, represents a rare chromosomal disorder. One of the mechanisms underlying the formation of uniparental disomy is the trisomy rescue, which concurrently results in low-level mosaicism. The diagnosis of mosaic aneuploidies poses significant challenges due to the limited sensitivity and resolution of conventional cytogenetic methods, which often fail to detect low-level mosaicism. Additionally, the variable distribution of cell lines within the patient’s tissues, as well as the heterogeneity of samples derived from the same tissue, complicates the precise determination of the impact of mosaic trisomy on the phenotypic expression. Phenotypic manifestations associated with mosaic trisomy 9 are characterized by considerable variability. During the prenatal period, intrauterine growth restriction is frequently observed in cases of this chromosomal abnormality, although this finding is not pathognomonic for the condition. In liveborn infants with trisomy 9 mosaicism, characteristic phenotypic features may include craniofacial anomalies (such as micrognathia and ear malformations), scoliosis, low-set ears, feeding and respiratory difficulties, hip dysplasia, seizures, and developmental delays. To establish a diagnosis in a patient presenting with multiple dysembryogenic stigmata and psychomotor retardation, a comprehensive molecular cytogenetic analysis was conducted. This included high-resolution chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) using targeted DNA probes. CMA identified regions of loss of heterozygosity (LOH) on chromosome 9, indicative of uniparental disomy, and suggested the presence of low-level mosaicism for trisomy 9. Subsequent FISH analysis of cultured lymphocytes, employing DNA probes specific to various regions of chromosome 9, confirmed the low-level mosaicism for trisomy 9. The results of our study are consistent with the idea that mosaicism for chromosome 9, particularly when combined with uniparental disomy, constitutes a complex genetic anomaly that can lead to a spectrum of phenotypic manifestations, including developmental delay, growth abnormalities, and behavioral anomalies. CMA and FISH are highly effective methods for the diagnosis of uniparental disomy and low-level mosaicism involving chromosome 9.