Pair analysis and custom array CGH can detect a small copy number variation in COQ6 gene

Area of Science:

• Genetics
• Molecular Biology
• Pediatric Nephrology

Background:

• Next-generation sequencing (NGS) has advanced genetic diagnostics for steroid-resistant nephrotic syndrome (SRNS).
• However, NGS fails to detect causative gene mutations in approximately 70% of SRNS cases, often due to non-genetic factors or limitations in detecting copy number variations (CNVs).

Observation:

• This study investigated an infantile nephrotic syndrome case using NGS, NGS data-dependent pair analysis, and custom array comparative genomic hybridization (aCGH).
• NGS alone identified a known pathogenic heterozygous missense mutation in the COQ6 gene.

Findings:

• Pair analysis and aCGH successfully detected a heterozygous exon 1-2 deletion (a CNV) in the COQ6 gene, which was missed by NGS alone.
• This comprehensive approach enabled the identification of compound heterozygous variants in COQ6.

Implications:

• The successful detection of CNVs in the COQ6 gene highlights the importance of complementary analytical methods beyond standard NGS.
• Early diagnosis and treatment with coenzyme Q10 (CoQ10) for COQ6-related SRNS can lead to complete remission and potentially delay the need for dialysis.