Pollitt syndrome patients carry mutation in TTDN1

Area of Science:

• Genetics
• Genomics
• Molecular Biology

Background:

• Pollitt syndrome (MIM #275550) presents with symptoms similar to non-photosensitive trichothiodystrophy (TTD).
• Previous investigations excluded mutations in the TTDN1/C7orf11 gene using Sanger sequencing.

Purpose of the Study:

• To identify the causative genetic mutation in a family affected by Pollitt syndrome.
• To demonstrate the utility of complete human genome sequencing in diagnosing rare genetic disorders.

Main Methods:

• Complete human genome sequencing was performed on a family with Pollitt syndrome.
• A homozygous single-base pair deletion in the TTDN1/C7orf11 gene was identified.
• The identified mutation (C326delA) was validated using conventional DNA sequencing.

Main Results:

• A novel homozygous deletion (C326delA) in the TTDN1/C7orf11 gene was found to cause Pollitt syndrome.
• This mutation leads to a frame shift at amino acid 93, consistent with non-photosensitive TTD.
• The inheritance pattern of the mutation confirmed its causative role in the affected family.

Conclusions:

• Complete human genome sequencing is effective in identifying causative mutations for rare genetic disorders like Pollitt syndrome.
• The study identified a previously overlooked mutation in the TTDN1/C7orf11 gene.
• Advanced sequencing technologies can redefine the understanding of genetic variations in Mendelian disorders.