The ATRX splicing variant c.21-1G>A is asymptomatic

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• Cockayne syndrome is a rare, severe genetic disorder.
• Alpha thalassemia X-linked intellectual disability syndrome (ATR-X) is associated with ATRX gene mutations.
• The role of ATRX and ERCC6 in DNA repair and transcription is critical.

Purpose of the Study:

• To investigate the genetic basis of Cockayne syndrome in a patient.
• To identify specific variants in the ATRX and ERCC6 genes.
• To understand the molecular consequences of identified variants.

Main Methods:

• Exome sequencing was performed on the patient's DNA.
• Bioinformatic analysis was used to identify genetic variants.
• Splicing prediction tools were utilized to assess the impact of the ATRX variant.

Main Results:

• A novel ATRX variant, c.21-1G>A, was identified, affecting the splicing acceptor site of intron 1.
• This ATRX variant leads to exon 2 deletion and premature termination (NM_000489.6: c.21_133del p.S7Rfs*1).
• Variants in the ERCC6 gene were also detected in the patient.

Conclusions:

• The identified ATRX variant is a potential cause of Cockayne syndrome in this patient.
• Despite the predicted truncation, a slightly shorter but functional ATRX protein may be produced from the start codon in exon 3.
• Co-occurrence of ERCC6 variants warrants further investigation into their combined effect.