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

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.

SUBMITTER: Wang C

PROVIDER: S-EPMC7549555 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Wang Chen C Xu Yufei Y Qing Yanrong Y Yao Ruen R Li Niu N Wang Xiumin X Yu Tingting T Wang Jian J

Molecular genetics & genomic medicine 20200810 10

<h4>Background</h4>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.<h4>Methods</h4>In this study, we analyzed the clinical and genetic data of five unrelated TRPS patients. They were suspected of having TRP ...[more]

PMID: 33073934

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Project description:BackgroundTricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial and skeletal abnormalities, while non-ossifying fibroma (NOF) is a common benign bone tumour in children and adolescents. To date, no case of TRPS coexisting with NOF has been reported. This report presents a 12-year-old girl who had the characteristic features of tricho-rhino-phalangeal syndrome and non-ossifying fibroma with a fibula fracture.Case presentationA 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of brachydactyly and a right fibula fracture. Clinical examination revealed sparse scalp hair, a characteristic bulbous pear-shaped nose, and brachydactyly with significant shortening of the fourth metatarsal. Neither intellectual disability nor multiple exostoses were observed. Radiography of both hands showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Genetic analysis of TRPS1 identified a heterozygous germline sequence variant (p.Ala932Thr) in exon 6 in the girl and her father. Approximately 1 month before being admitted to our department, the girl experienced a minor fall and suffered a fracture of the proximal fibula in the right lower limb. The pathological cytological diagnosis of the osteolytic lesion was NOF. Ten months following the surgery, the lesion on the proximal fibula of the girl disappeared.ConclusionsIn conclusion, the present study is the first to report a rare case of NOF with a pathologic fracture in the fibula of a girl with TRPS. The identification of a missense mutation, (p.Ala932Thr), in exon 6 of TRPS1 in this kindred further suggested that the patient had type I TRPS and indicated that mutations in this exon may be correlated with more pronounced features of the syndrome. Radiological techniques and genetic analysis played key roles in the definitive diagnosis.

Dataset Information

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

Publications

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

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