An intragenic duplication of leading to abnormal transcripts and causing trichorhinophalangeal syndrome type I.

Trichorhinophalangeal syndrome type I (TRPSI) is a rare disorder that causes distinctive ectodermal, facial, and skeletal features affecting the hair (tricho-), nose (rhino-), and fingers and toes (phalangeal) and is inherited in an autosomal dominant pattern. TRPSI is caused by loss of function variants in , involved in the regulation of chondrocyte and perichondrium development. Pathogenic variants in include missense mutations and deletions with variable breakpoints, with only a single instance of an intragenic duplication reported to date. Here we report an affected individual presenting with a classic TRPSI phenotype who is heterozygous for a de novo intragenic ∼36.3-kbp duplication affecting exons 2-4 of Molecular analysis revealed the duplication to be in direct tandem orientation affecting the splicing of The aberrant transcripts are predicted to produce a truncated TRPS1 missing the nuclear localization signal and the GATA and IKAROS-like zinc-finger domains resulting in functional haploinsufficiency. Our study identifies a novel intragenic tandem duplication of and highlights the importance of molecular characterization of intragenic duplications.