Trichothiodystrophy hair shafts display distinct ultrastructural features

Area of Science:

• Genetics
• Cell Biology
• Dermatology

Background:

• Trichothiodystrophy (TTD) is a rare genetic disorder affecting DNA repair and transcription.
• Mutations in the ERCC2 (XPD) gene are a known cause of TTD.
• Hair shaft abnormalities are a clinical feature of TTD.

Purpose of the Study:

• To investigate the ultrastructural hair shaft defects in TTD patients with ERCC2 (XPD) mutations.
• To correlate hair shaft morphology with the underlying genetic defect.

Main Methods:

• Transmission electron microscopy (TEM) was used to examine hair shafts from three TTD patients.
• Hair shafts underwent partial disulfide bond reduction and SDS treatment to improve visualization.
• Comparative analysis was performed between TTD and normal hair shafts.

Main Results:

• TTD hair shafts exhibited aberrant cuticle cells, including abnormal marginal bands and exocuticle layers.
• Cortical cells showed differential staining (light/dark) and significantly shorter keratin macrofibrils.
• Heterogeneity in these abnormalities was observed within samples and along individual hair shafts.

Conclusions:

• The findings suggest a paucity of high-sulfur proteins, like keratin-associated proteins, in TTD hair shafts.
• A profound imbalance in protein content and organization contributes to the observed hair shaft defects in TTD.
• ERCC2 (XPD) gene mutations lead to significant structural hair shaft abnormalities via impaired DNA repair pathways.