1. An intragenic duplication of TRPS1 leading to abnormal transcripts and causing trichorhinophalangeal syndrome type I.
- Author
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Zepeda-Mendoza CJ, Cousin MA, Basu S, Jenkinson G, Oliver G, Pittock ST, Baughn LB, Klee EW, and Babovic-Vuksanovic D
- Subjects
- Aged, Child, DNA-Binding Proteins genetics, Exons genetics, Family, Female, Gene Duplication genetics, Hair Diseases etiology, Humans, Langer-Giedion Syndrome etiology, Male, Middle Aged, Mutation, Mutation, Missense genetics, Pedigree, Phenotype, RNA Splicing genetics, Repressor Proteins metabolism, Sequence Deletion genetics, Transcription Factors genetics, Zinc Fingers genetics, Fingers abnormalities, Hair Diseases genetics, Langer-Giedion Syndrome genetics, Nose abnormalities, Repressor Proteins genetics
- Abstract
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 TRPS1 , involved in the regulation of chondrocyte and perichondrium development. Pathogenic variants in TRPS1 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 TRPS1 Molecular analysis revealed the duplication to be in direct tandem orientation affecting the splicing of TRPS1 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 TRPS1 haploinsufficiency. Our study identifies a novel intragenic tandem duplication of TRPS1 and highlights the importance of molecular characterization of intragenic duplications., (© 2019 Zepeda-Mendoza et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2019
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