A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital...

Area of Science:

• Genomics
• Human Genetics
• Rare Diseases

Background:

• Structural variants (SVs) are challenging to detect but crucial for understanding rare diseases.
• A family with a five-generation history of congenital heart defects presented with a complex 9p24 rearrangement.

Approach:

• Integrated multiple genomic analyses: karyotype, CMA, FISH, WGS, RNA-seq, and OGM.
• Utilized WGS and OGM to elucidate the complex 9p24 structural variant structure.
• Confirmed a chimeric transcript involving KANK1/DMRT1 loci via RNA-seq.

Key Points:

• A complex SV involving three duplications and an inversion at 9p24 was identified.
• The rearrangement results in a chimeric transcript of KANK1/DMRT1.
• The identified genomic rearrangement acts as a genetic biomarker for familial congenital defects.

Conclusions:

• A comprehensive genomic approach successfully characterized a complex 9p24 rearrangement.
• The study identified a genetic biomarker for a familial congenital trait.
• This biomarker facilitated embryo selection, impacting reproductive outcomes for affected families.