A Japanese trichothiodystrophy patient with XPD mutations

Area of Science:

• Genetics
• Molecular Biology
• Dermatology

Background:

• Trichothiodystrophy (TTD) is a rare autosomal recessive disorder.
• Characterized by sulfur-deficient brittle hair, ichthyosis, developmental delays, and infections.
• Photosensitivity occurs in TTD due to nucleotide excision repair defects.

Observation:

• A severely affected Japanese TTD patient with XPD mutations was identified.
• The patient's father presented with ichthyotic skin.
• Paternal allele mutation: Arg-722 to Trp (R722W).

Findings:

• Maternal allele mutation: a novel 3-bp deletion (nucleotides 67-69) causing Ser-23 deletion in XPD.
• The identified alterations were confirmed as causative mutations for TTD.
• Expression studies validated the pathogenicity of the novel mutation.

Implications:

• This case expands the known spectrum of XPD mutations in TTD.
• Suggests potential underdiagnosis of TTD in Asian populations.
• Highlights the importance of genetic analysis for TTD diagnosis.