A new mutation in the gene ROR2 causes brachydactyly type B1

Huang, Dan; Jiang, Shujuan; Zhang, Yuanyuan; Liu, Xiaoliang; Zhang, Jiubin; He, Rong

doi:10.1016/j.gene.2014.06.035

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…22 Wnt5a was also found to be necessary for kidney development in both mouse and zebrafish phenocopied to RS patients. 5,15,16,23,24 Moreover, the NXN gene encodes nucleoredoxin, a regulator of the Wnt/PCP pathway through binding with DVL. Nxn −/− mouse models showed abnormal differentiation of osteoblastic cells, craniofacial abnormalities with a shortened nose, and cleft palate partially recapitulating the RS subjects' phenotype.…”

Section: Introductionmentioning

confidence: 99%

“…5,7,12,13 Heterozygous mutations in the ROR2 gene is also associated with a distinct syndrome, the autosomal dominant brachydactyly type B1 (BDB1, OMIM 113000); however, a small phenotypic overlap has to be noted. 14,15 Homozygous mutations in ROR2 and WNT5A were found to impair the WNT5A/ROR2 signal pathway resulting in skeletal abnormalities and other features characteristic of RS. 8,[16][17][18] RS phenotype has been discussed comprehensively in zebrafish, Xenopus, and mouse models.…”

Section: Introductionmentioning

confidence: 99%

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Tomographic Study of the Malformation Complex in Correlation With the Genotype in Patients With Robinow Syndrome: Review Article

Kaissi

Kenis

Shboul

et al. 2020

Journal of Investigative Medicine High Impact Case Reports

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We aimed to understand the etiology behind the abnormal craniofacial contour and other clinical presentations in a number of children with Robinow syndrome. Seven children with Robinow syndrome were enrolled in this study (autosomal recessive caused by homozygous mutations in the ROR2 gene on chromosome 9q22, and the autosomal dominant caused by heterozygous mutation in the WNT5A gene on chromosome 3p14). In the autosomal recessive (AR) group, the main clinical presentations were intellectual, disability, poor schooling achievement, episodes of headache/migraine, and poor fine motor coordinative skills, in addition to massive restrictions of the spine biomechanics causing effectively the development of kyposcoliosis and frequent bouts of respiratory infections. Three-dimensional reconstruction computed tomography scan revealed early closure of the metopic and the squamosal sutures of skull bones. Massive spinal malsegmentation and unsegmented spinal bar were noted in the AR group. In addition to severe mesomelia and camptodactyly, in the autosomal dominant (AD) group, no craniosynostosis but few Wormian bones and the spine showed limited malsegemetation, and no mesomelia or camptodactyly have been noted. We wish to stress that little information is available in the literature regarding the exact pathology of the cranial bones, axial, and appendicular malformations in correlation with the variable clinical presentations in patients with the 2 types of Robinow syndrome.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tomographic Study of the Malformation Complex in Correlation With the Genotype in Patients With Robinow Syndrome: Review Article

Kaissi

Kenis

Shboul

et al. 2020

Journal of Investigative Medicine High Impact Case Reports

View full text Add to dashboard Cite

show abstract

“…ROR2 was initially found to play critical role in embryo development, like heart, lung, limbs and brain [5, 28, 29]. Mutations of ROR2 could result in human genetic disorders, like Robinow syndrome and brachydactyly type B (BDB) [30–33]. However, the role of ROR2 in human adult tissues has been hardly researched.…”

Section: Discussionmentioning

confidence: 99%

ROR2 induces cell apoptosis via activating IRE1α/JNK/CHOP pathway in high-grade serous ovarian carcinoma in vitro and in vivo

Liu

Shi

et al. 2019

J Transl Med

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BackgroundEpithelial ovarian cancer (EOC) is the most lethal cancer in female genital tumors. New disease markers and novel therapeutic strategies are urgent to identify considering the current status of treatment. Receptor tyrosine kinases family plays critical roles in embryo development and disease progression. However, ambivalent research conclusions of ROR2 make its role in tumor confused and the underlying mechanism is far from being understood. In this study, we sought to clarify the effects of ROR2 on high-grade serous ovarian carcinoma (HGSOC) cells and reveal the mechanism.MethodsImmunohistochemistry assay and western-blot assay were used to detect proteins expression. ROR2 overexpression adenovirus and Lentivirus were used to create ROR2 overexpression model in vitro and in vivo, respectively. MTT assay, colony formation assay and transwell assay were used to measure the proliferation, invasion and migration ability of cancer cells. Flow cytometry assay was used to detect cell apoptosis rate. Whole transcriptome analysis was used to explore the differentially expressed genes between ROR2 overexpression group and negative control group. SiRNA targeted IRE1α was used to knockdown IRE1α. Kira6 was used to inhibit phosphorylation of IRE1α.ResultsExpression of ROR2 was significantly lower in HGSOC tissues compared to normal fallopian tube epithelium or ovarian surface epithelium tissues. In HGSOC cohort, patients with advanced stages or positive lymph nodes were prone to express lower ROR2. Overexpression of ROR2 could repress the proliferation of HGSOC cells and induce cell apoptosis. RNA sequencing analysis indicated that ROR2 overexpression could induce unfold protein response. The results were also confirmed by upregulation of BIP and phosphorylated IRE1α. Furthermore, pro-death factors like CHOP, phosphorylated JNK and phosphorylated c-Jun were also upregulated. IRE1α knockdown or Kira6 treatment could reverse the apoptosis induced by ROR2 overexpression. Finally, tumor xenograft experiment showed ROR2 overexpression could significantly repress the growth rate and volume of transplanted tumors.ConclusionsTaken together, ROR2 downregulation was associated with HGSOC development and progression. ROR2 overexpression could repress cell proliferation and induce cell apoptosis in HGSOC cells. And the underlying mechanism might be the activation of IRE1α/JNK/CHOP pathway induced by ROR2.

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“…Analysis of Wnt expression in the developing mouse limb by in situ hybridization suggests that Wnt5a , Wnt5b , and Wnt11 are expressed in the mesenchyme of developing limb buds before E12.5 . In human, mutations in WNT5A and its receptor ROR2 have been identified in two congenital skeletal disorders: Robinow syndrome and Brachydactyly type B . These skeletal defects are recapitulated in Wnt5a and Ror2 knockout mice, as exhibited by truncation of the proximal limb skeleton .…”

Section: Discussionmentioning

confidence: 99%

Disruption of Wnt production in Shh lineage causes bone malformation in mice, mimicking human Malik–Percin‐type syndactyly

et al. 2018

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Here, we show that Shh-Cre-mediated deletion of Wntless, the Wnt cargo protein, in mouse posterior limb mesenchyme causes bone syndactyly of the 3rd and 4th digits, resembling the human Malik-Percin type. The Shh descendants gradiently distributed from digit 5 to posterior half of digit 3 in wild-type limbs, however, they abnormally increased in posterior digit 3 in Wntless . Wntless limbs displayed altered expression of hedgehog pathway genes and impaired noncanonical Wnt signaling activity. We further showed that the anterior limb mesenchymal cells in the Wls served as a source of Wnt5a to reorientate the adjacent Wls-lacking Shh lineage cells to move anteriorly and subsequently led to syndactyly, suggesting that aberrant mesenchymal cell movement/condensation may underlie the pathogenesis of syndactyly.

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A new mutation in the gene ROR2 causes brachydactyly type B1

Cited by 11 publications

References 29 publications

Tomographic Study of the Malformation Complex in Correlation With the Genotype in Patients With Robinow Syndrome: Review Article

Tomographic Study of the Malformation Complex in Correlation With the Genotype in Patients With Robinow Syndrome: Review Article

ROR2 induces cell apoptosis via activating IRE1α/JNK/CHOP pathway in high-grade serous ovarian carcinoma in vitro and in vivo

Disruption of Wnt production in Shh lineage causes bone malformation in mice, mimicking human Malik–Percin‐type syndactyly

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