Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia
Pierre K Boerkoel1, Katherine Dixon2,3, Carrie Fitzsimons4
1MD Undergraduate Program, University of British Columbia, Vancouver, British Columbia, Canada.
American Journal of Medical Genetics. Part A
|February 5, 2022
Summary
A complex rearrangement on chromosome 13q in a newborn with anophthalmia provides new insights into the genetic causes of microphthalmia, anophthalmia, and coloboma (MAC) spectrum disorders.
Area of Science:
- Genetics
- Developmental Biology
- Ophthalmology
Background:
- Microphthalmia, anophthalmia, and coloboma (MAC) are congenital eye disorders with diverse genetic and environmental causes.
- Structural and copy number variants on chromosome 13 are linked to MAC, but specific disease-causing regions remain unclear.
Observation:
- A newborn with syndromic degenerative anophthalmia presented with a complex de novo rearrangement on chromosome 13q.
- Long-read genome sequencing revealed a duplication-triplication/inversion-duplication and terminal deletion, with breakpoint analysis suggesting microhomology-mediated break-induced replication.
Findings:
- The study refines a potential dosage-sensitive critical region on chromosome 13q associated with MAC disorders.
- This complex rearrangement offers a high-resolution view of pathogenic mechanisms in 13q-linked eye abnormalities.
Implications:
- Findings may enhance understanding of the molecular etiology of MAC spectrum disorders.
- Identification of critical regions can aid in genetic diagnosis and counseling for affected families.
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