Neurodevelopmental delay, musculoskeletal disorders and dysmorphia associated with a novel pathogenic interstitial deletion of chromosome 10q21.1q21.3

Background Previous reports of distal deletions in chromosome 10q in patients have described distinct facial features combined with other neurodevelopmental abnormalities, including intellectual disability. However, the association of interstitial deletions in chromosome 10q with global developmental delay, musculoskeletal abnormalities, and dysmorphic features has not been previously reported. Methods Genetic testing using whole exome sequencing (WES) was performed on three patients with neurodevelopmental delay, musculoskeletal abnormalities and dysmorphic features. Sequencing reads were aligned to the human genome build GRCh37/UCSC hg19 and analysed for both sequence and copy number variants. Results WES identified similar interstitial deletions in the 10q21.1q21.3 locus in all three patients. The deleted region includes online Mendelian inheritance in man (OMIM)-annotated genes with clinical significance, such as ANK3 (*600465), JMJD1C (*604503), EGR2 (*129010), BICC1 (*614295), ZNF365 (*607818) and TFAM (*600438). Deletion of this region is considered pathogenic and is implicated in the aetiology of the clinical phenotypes observed in these patients. Conclusions This is the first report associating interstitial deletions in the 10q21.1q21.3 locus with neurodevelopmental delay, musculoskeletal abnormalities and dysmorphic features. Our findings highlight the clinical significance of this deleted region and suggest possible mechanisms underlying the observed pathological phenotypes.