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Background  Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the  TRPS1  gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the  TRPS1  gene, have been reported. A deregulated expression of  TRPS1  has been hypothesised as cause of the TRPS phenotype of these patients.    Case presentation  We report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3)  de novo  balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting  TRPS1  or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of  TRPS1 , and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA  LINC00536 , at approximately 300 kb from the  TRPS1  5’ end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325 kb from the  TRPS1  promoter.    Conclusions  We suggest that the disruption of the genomic architecture of  cis  regulatory elements downstream the  TRPS1  5′ region, combined with the translocation of a novel enhancer element nearby  TRPS1 , might be the pathogenetic mechanism underpinning the proband’s phenotype. The clinical and genetic characterisation of the present subject allowed us to make a genetic diagnosis in the context of a known syndrome, contributing to a better comprehension of the complex transcriptional regulation of  TRPS1  and TRPS ethiopathogenesis.

New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene