Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia
Abstract Background Wnt signaling pathway plays an important role in promoting ostergenesis. WNT1 mutations have been considered as a major cause of ostergenesis imperfect (OI). We identified an OI patient with pathogenic consanguineous‐derived homozygous WNT1 missense mutation. Methods We designed...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1350 |
| _version_ | 1797301065191784448 |
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| author | Peng Chen Jiaxi Chen Zhantao Yang Yang Lu Liping Shen Kai Zhou Shenyi Ye Bo Shen |
| author_facet | Peng Chen Jiaxi Chen Zhantao Yang Yang Lu Liping Shen Kai Zhou Shenyi Ye Bo Shen |
| author_sort | Peng Chen |
| collection | DOAJ |
| description | Abstract Background Wnt signaling pathway plays an important role in promoting ostergenesis. WNT1 mutations have been considered as a major cause of ostergenesis imperfect (OI). We identified an OI patient with pathogenic consanguineous‐derived homozygous WNT1 missense mutation. Methods We designed and applied a panel of known 261 genes associated with hereditary bone diseases for targeted next‐generation sequencing to examine clinically diagnosed OI patients. Detected mutations were confirmed by Sanger sequencing. Results The female proband presented with severe OI with low bone density, multiple long bone fractures, short stature, and absence of dentinogenesis imperfect and brain malformation. She had congenital ptosis and exotropia with her left eye, and absence of blue sclera. The proband came from a consanguineous family and had a homozygous WNT1 missense mutation (c.677C>T, (p.S226L)). In addition, three other compound heterozygous mutations (c.1729C>T in FKBP10, c.1958A>C in FGFR3, c.760G>C in TRPV4) were also detected in her family members. Conclusion We report the first identified case of consanguineous derived homozygous WNT1 mutation leading to severe osteogenesis imperfecta with congenital ptosis and exotropia. |
| first_indexed | 2024-03-07T23:16:02Z |
| format | Article |
| id | doaj.art-7aa94b3c4e7c4970ac42ee60bf7dd1f8 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:02Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-7aa94b3c4e7c4970ac42ee60bf7dd1f82024-02-21T11:08:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1350Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropiaPeng Chen0Jiaxi Chen1Zhantao Yang2Yang Lu3Liping Shen4Kai Zhou5Shenyi Ye6Bo Shen7Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaContinuing Medical Education and Research Center Dian Diagnostics Group Co., Ltd. Hangzhou P.R. ChinaTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaTaizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University Lin Hai P.R. ChinaAbstract Background Wnt signaling pathway plays an important role in promoting ostergenesis. WNT1 mutations have been considered as a major cause of ostergenesis imperfect (OI). We identified an OI patient with pathogenic consanguineous‐derived homozygous WNT1 missense mutation. Methods We designed and applied a panel of known 261 genes associated with hereditary bone diseases for targeted next‐generation sequencing to examine clinically diagnosed OI patients. Detected mutations were confirmed by Sanger sequencing. Results The female proband presented with severe OI with low bone density, multiple long bone fractures, short stature, and absence of dentinogenesis imperfect and brain malformation. She had congenital ptosis and exotropia with her left eye, and absence of blue sclera. The proband came from a consanguineous family and had a homozygous WNT1 missense mutation (c.677C>T, (p.S226L)). In addition, three other compound heterozygous mutations (c.1729C>T in FKBP10, c.1958A>C in FGFR3, c.760G>C in TRPV4) were also detected in her family members. Conclusion We report the first identified case of consanguineous derived homozygous WNT1 mutation leading to severe osteogenesis imperfecta with congenital ptosis and exotropia.https://doi.org/10.1002/mgg3.1350congenital ptosis and exotropiahomozygous mutationosteogenesis imperfectWNT1 |
| spellingShingle | Peng Chen Jiaxi Chen Zhantao Yang Yang Lu Liping Shen Kai Zhou Shenyi Ye Bo Shen Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia Molecular Genetics & Genomic Medicine congenital ptosis and exotropia homozygous mutation osteogenesis imperfect WNT1 |
| title | Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia |
| title_full | Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia |
| title_fullStr | Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia |
| title_full_unstemmed | Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia |
| title_short | Consanguineous‐derived homozygous WNT1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia |
| title_sort | consanguineous derived homozygous wnt1 mutation results in osteogenesis imperfect with congenital ptosis and exotropia |
| topic | congenital ptosis and exotropia homozygous mutation osteogenesis imperfect WNT1 |
| url | https://doi.org/10.1002/mgg3.1350 |
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