Terminal 4q duplication and extended 10q deletion in a preterm infant with linear growth restriction: transcriptomic...

Distal duplication 4q syndrome and distal 10q26 deletion syndrome are rare chromosomal abnormalities associated with complex and overlapping phenotypes. Most cases result from unbalanced inheritance of a parental translocation, yet the specific contributions of each chromosomal segment to the clinical phenotype remain poorly defined.

We report on a male preterm infant born at 28 + 6 weeks' gestation who carried a derivative chromosome 10 due to a paternally inherited unbalanced translocation t(4;10)(q31.22;q26.13), leading to a 42.46 Mb duplication of 4q31.22-q35.2 and a 10.77 Mb deletion of 10q26.13-q26.3. The patient presented with severe postnatal linear growth restriction, delayed neurodevelopment, a giant umbilical hernia, bilateral renal hypoplasia, and relative overweight. Thumb anomalies were absent.

Genetic analyses included chromosomal microarray, conventional karyotyping, fluorescence in situ hybridization (FISH), and transcriptome profiling from peripheral blood mononuclear cells.

Gene expression analysis confirmed reduced expression of established 10q26-related genes, including FGFR2, EMX2, WDR11, NSMCE4A, and EBF3, and additionally identified reduced expression of DMBT1, CUZD1, CTBP2, CHST15, OAT, and LHPP. These genes are implicated in epithelial-mesenchymal signaling, extracellular matrix organization, developmental regulation, and metabolic pathways. Regional transcriptomic analysis further supported dosage-associated effects, with lower averaged expression across genes represented on the array within the deleted 10q26.13-10q26.3 interval and higher averaged expression across genes within the duplicated 4q31.22-4q35.2 interval compared with the reference dataset. Adjacent flanking regions did not show comparable directional shifts, supporting the interpretation that the observed transcriptional changes were regionally aligned with the structural chromosomal imbalance rather than reflecting a global PBMC expression difference.

This case illustrates how extended terminal deletions of 10q can disrupt key structural and metabolic gene networks. To our knowledge, this is the first transcriptomic characterization of a 10.77 Mb deletion in the 10q26.13-q26.3 region together with a large terminal 4q duplication. Integrating functional transcriptomics with clinical and cytogenetic data may enhance our understanding of rare chromosomal disorders and inform individualized management, including reproductive counseling and longitudinal clinical follow-up.