An intragenic duplication of TRPS1 leading to abnormal transcripts and causing trichorhinophalangeal syndrome type I.
Cold Spring Harb Mol Case Stud
; 5(6)2019 12.
Article
em En
| MEDLINE
| ID: mdl-31662300
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 â¼36.3-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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Síndrome de Langer-Giedion
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Nariz
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Dedos
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Doenças do Cabelo
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article