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Background <p>Vohwinkel Syndrome (VS) is a rare autosomal dominant skin disorder with two main mutation types: the classic form caused by <i>GJB2</i> gene mutations and loricrin keratoderma (LK) linked to <i>LOR</i> gene mutations. LK typically lacks hearing loss and often presents at birth as collodion baby syndrome.</p> Methods <p>A 7-year-old male proband presenting with congenital thickening of the palms and soles was admitted to Başakşehir Çam and Sakura City Hospital. Whole-exome sequencing was performed from a whole blood sample using the MGI-400 platform, and common or benign mutations were excluded. Segregation analysis confirmed a pathogenic <i>LOR</i> mutation. Wild-type and mutant loricrin structures were modeled using I-TASSER and refined with ModRefiner. Protein interactions were analyzed via STRING, and docking with TGase 3 was performed using HDOCK. Structural visualization was completed using UCSF Chimera.</p> Results <p>A specific <i>LOR</i> mutation [NM_000427.3 c.684dup p.(Ser229ValfsTer107)] was identified, associated with palmoplantar keratoderma, ichthyosis-like plaques on the elbows and knees, anhidrosis, and absence of dental abnormalities, consistent with typical loricrin keratoderma (LK) cases. In silico analysis revealed that wild-type loricrin binds transglutaminase 3 (Tgase 3) with a lower score, and serine interactions present in normal loricrin were absent in the mutant form. Frameshift mutations also reduced glycine motifs critical for epidermal protein organization and skin flexibility.</p> Conclusion <p>Genetic testing is essential for accurate diagnosis and differentiation of LK from other VS types. This case highlights the importance of genetic screening for early diagnosis and improved management, ultimately enhancing patient care in rare populations.</p>

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A rare case of LORICRIN gene c.684dup mutation associated with Vohwinkel syndrome in a Turkish patient, in silico analysis and literature review

  • 期刊论文

  • 发表日期：

    2025年11月27日

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  • Cuneyd Yavas,
  • Emir Nekay,
  • Asmaa Abuaisha,
  • Yusuf Seflekci,
  • Kubra Turegun,
  • Zafer Turkoglu,
  • Eriscan Melih Kirsoy,
  • Mustafa Dogan

摘要

Background

Vohwinkel Syndrome (VS) is a rare autosomal dominant skin disorder with two main mutation types: the classic form caused by GJB2 gene mutations and loricrin keratoderma (LK) linked to LOR gene mutations. LK typically lacks hearing loss and often presents at birth as collodion baby syndrome.

Methods

A 7-year-old male proband presenting with congenital thickening of the palms and soles was admitted to Başakşehir Çam and Sakura City Hospital. Whole-exome sequencing was performed from a whole blood sample using the MGI-400 platform, and common or benign mutations were excluded. Segregation analysis confirmed a pathogenic LOR mutation. Wild-type and mutant loricrin structures were modeled using I-TASSER and refined with ModRefiner. Protein interactions were analyzed via STRING, and docking with TGase 3 was performed using HDOCK. Structural visualization was completed using UCSF Chimera.

Results

A specific LOR mutation [NM_000427.3 c.684dup p.(Ser229ValfsTer107)] was identified, associated with palmoplantar keratoderma, ichthyosis-like plaques on the elbows and knees, anhidrosis, and absence of dental abnormalities, consistent with typical loricrin keratoderma (LK) cases. In silico analysis revealed that wild-type loricrin binds transglutaminase 3 (Tgase 3) with a lower score, and serine interactions present in normal loricrin were absent in the mutant form. Frameshift mutations also reduced glycine motifs critical for epidermal protein organization and skin flexibility.

Conclusion

Genetic testing is essential for accurate diagnosis and differentiation of LK from other VS types. This case highlights the importance of genetic screening for early diagnosis and improved management, ultimately enhancing patient care in rare populations.