Abstract
Craniotubular dysplasia, Ikegawa type (CTDI) is a rare autosomal recessive skeletal dysplasia characterized by hyperostosis of the calvaria and skull base, metadiaphyseal undermodeling of the long tubular bones, and mild shortening and diaphyseal broadening of the short tubular bones. Its causal gene is TMEM53. Six CTDI families have been reported; however, its clinical course and prognosis still remain to be determined. Here, we report two Iranian siblings carrying a novel homozygous missense variant of TMEM53. The affected individuals were referred for progressive severe visual loss of unknown cause. The patient had severe optic atrophy and optic canal narrowing. Radiographic evaluation suggested the diagnosis of CTDI, which was confirmed by the identification of TMEM53 variant (c.704G > T, p.R235L) co-segregating in the consanguineous family. The proband underwent trans-nasal endoscopic optic canal decompression and showed remarkable improvement in visual acuity and daily visual tasks. We recommend early comprehensive clinical and genetic evaluation followed by proper treatment to improve the prognosis of CTDI.
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Acknowledgements
We thank the patients and their families for their help to the study.
Funding
This study was supported by National Natural Science Foundation of China (Grant No. 82471900, L.G.), Supporting Program of Innovation Capability of Shaanxi Province (2024CX-GXPT-40, L.G.), Provincial Talent Research Support Fund (71240000000131, L.G.), Shaanxi Provincial Project for Innovation Capacity Improvement of Health Research (2024PT-03, R.Q.), Provincial Key Industry Innovation Chain (2024SF-ZDCYL-04-05, R.Q.), and Young Talent Support Plan from Xi’an Jiaotong University (YX6J033, L.G.).
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Long Guo and Niloofar Pirmarzdashti designed the study. Kaitao Ren, Niloofar Pirmarzdashti, Farzad Pakdel, Lin Wang, Moosa Sadrhosseini, Farzane Abassi, Yao Xiong, Jiaqi Han, Lianying Jiao carried out the research. Kaitao Ren, Niloofar Pirmarzdashti, Farzad Pakdel, Jinhui Zhu, Wanqi Liu, Lin Wang, Moosa Sadrhosseini, Farzane Abassi, Yao Xiong, Jiaqi Han, Lianying Jiao, Gen Nishimura, Takahiro Yamada analyzed and interpreted data. Kaitao Ren, Niloofar Pirmarzdashti, Farzad Pakdel drafted the manuscript. Long Guo and Rong Qiang revised it. All authors read and approved the final manuscript.
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Ren, K., Pirmarzdashti, N., Pakdel, F. et al. A novel missense pathogenic variants of TMEM53 in an Iranian family with craniotubular dysplasia, Ikegawa type. J Hum Genet 70, 195–198 (2025). https://doi.org/10.1038/s10038-025-01319-z
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DOI: https://doi.org/10.1038/s10038-025-01319-z
