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TRPS1 mutation detection in Chinese patients with Tricho‐rhino‐phalangeal syndrome and identification of four novel mutations.

Authors :
Wang, Chen
Xu, Yufei
Qing, Yanrong
Yao, Ruen
Li, Niu
Wang, Xiumin
Yu, Tingting
Wang, Jian
Source :
Molecular Genetics & Genomic Medicine; Oct2020, Vol. 8 Issue 10, p1-9, 9p
Publication Year :
2020

Abstract

Background: Tricho‐rhino‐phalangeal syndrome (TRPS) is a rare autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, a pear‐shaped nose, and cone‐shaped epiphyses. This condition is caused by haploinsufficiency or dominant‐negative effect of the TRPS1 gene. Methods: In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRPS on the basis of clinical and radiological features including typical hair and facial features, as well as varying degrees of skeletal abnormalities. Next‐generation sequencing was performed to identify variants of the TRPS1 gene in the five patients. Results: In patient 1, we found a novel mutation at c.1338C>A (p.Tyr446*) (de novo). Patient 2 had a novel phenotype of hydrocephaly and Arnold–Chiari syndrome and we also found a maternally inherited novel mutation at c.2657C>A (p.Ser886*). Patient 3 had a de novo novel mutation at c.2726G>C (p.Cys909Ser) leading to more severe phenotypes. Patient 4 had a paternally inherited known mutation at c.2762G>A (p.Arg921Gln). Patient 5 with a novel phenotype of hepatopathy had a novel deletion at [GRCh37] del(8)(q23.3‐q24.11) chr8:g.116,420,724‐119,124,058 (over 2,700 kb). In addition, the patient 3 who harboring missense variants in the GATA binding domain of TRPS1 showed more severe craniofacial and skeletal phenotypes. Conclusions: We describe four novel mutations and two novel phenotypes in five patients. The mutational and phenotypic spectrum of TRPS is broadened by our study on TRPS mutations. Our results reveal the significance of molecular analysis of TRPS1 for improving the clinical diagnosis of TRPS. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
23249269
Volume :
8
Issue :
10
Database :
Complementary Index
Journal :
Molecular Genetics & Genomic Medicine
Publication Type :
Academic Journal
Accession number :
146395534
Full Text :
https://doi.org/10.1002/mgg3.1417