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A Novel Missense Pathogenic Variants of Tmem53 in an Iranian Family With Craniotubular Dysplasia, Ikegawa Type Publisher Pubmed



Ren K1 ; Pirmarzdashti N2 ; Pakdel F3, 4 ; Zhu J1 ; Liu W1 ; Wang L5 ; Sadrhosseini M6 ; Abassi F7 ; Xiong Y8 ; Han J9 ; Jiao L9 ; Nishimura G10 ; Yamada T11 ; Qiang R5 Show All Authors
Authors
  1. Ren K1
  2. Pirmarzdashti N2
  3. Pakdel F3, 4
  4. Zhu J1
  5. Liu W1
  6. Wang L5
  7. Sadrhosseini M6
  8. Abassi F7
  9. Xiong Y8
  10. Han J9
  11. Jiao L9
  12. Nishimura G10
  13. Yamada T11
  14. Qiang R5
  15. Guo L1, 5
Show Affiliations
Authors Affiliations
  1. 1. Department of Laboratory Animal Science, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
  2. 2. Pediatric Cell and Gene Therapy Research Center, Children’s Medical Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Oculo-Facial Plastic Surgery, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Center of Medical Genetics, Northwest Women’s and Children’s Hospital, Xi’an, China
  6. 6. Otorhinolaryngology Research Center, IKH Complex, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Growth and development research center, Children’s medical hospital, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. The Assisted Reproduction Center, Northwest Women’s and Children’s Hospital, Xi’an, China
  9. 9. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi’an Jiaotong University Health Science Center, Xi’an, China
  10. 10. Department of Radiology, Musashino-Yowakai Hospital, Tokyo, Japan
  11. 11. Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan

Source: Journal of Human Genetics Published:2025


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. © The Author(s), under exclusive licence to The Japan Society of Human Genetics 2025.