A Cohesin Subunit Variant Identified from a Peripheral Sclerocornea Pedigree

Area of Science:

• Ophthalmology
• Genetics
• Cell Biology

Background:

• Sclerocornea is a rare congenital disorder causing corneal opacification.
• This study investigates a nonconsanguineous Chinese family with multiple peripheral sclerocornea patients across three generations.
• The condition exhibits autosomal dominant inheritance.

Purpose of the Study:

• To identify the genetic basis of peripheral sclerocornea in the studied family.
• To investigate the functional consequences of the identified genetic variant.

Main Methods:

• Retrospective case series of a peripheral sclerocornea pedigree.
• Comprehensive ophthalmic examinations of 14 family members.
• Whole-exome sequencing to identify genetic alterations.
• Establishment of lymphoblastoid cell lines (LCLs) for functional studies.

Main Results:

• Six affected and eight unaffected individuals were examined.
• Affected individuals displayed peripheral corneal scleralization, reduced corneal diameter, and altered pachymetry.
• A RAD21 variant (R450C) was identified, segregating with the disease, but LCLs showed no mitosis or ploidy defects.

Conclusions:

• A RAD21 variant cosegregates with peripheral sclerocornea in this family.
• The findings exclude an association with cornea plana.
• RAD21's non-cell cycle regulatory functions may underlie peripheral sclerocornea pathogenesis.