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.
• Familial congenital heart defects (CHDs) often have complex genetic underpinnings.

Purpose of the Study:

• To elucidate a complex 9p24 rearrangement segregating in a family with CHDs across five generations.
• To characterize the genomic structure and identify potential disease mechanisms.

Main Methods:

• Combined genomic analysis including karyotype, CMA, FISH, GS, RNA-seq, and OGM.
• Breakpoint mapping and transcript analysis to define the SV structure.
• Genetic biomarker identification for reproductive applications.

Main Results:

• A complex 9p24 structural variant involving duplications, inversion, and SINE element insertion was identified.
• A chimeric transcript of KANK1/DMRT1 loci was formed by the rearrangement.
• The identified genetic biomarker facilitated successful embryo selection.

Conclusions:

• A comprehensive genomic approach successfully characterized a complex 9p24 rearrangement associated with familial CHDs.
• The study highlights the importance of advanced genomic tools for diagnosing rare diseases.
• The identified genetic biomarker offers reproductive options for affected families.