A new association between CDK5RAP2 microcephaly and congenital cataracts

Area of Science:

• Genetics
• Neurology
• Ophthalmology

Background:

• Primary microcephaly type 3 is a rare genetic disorder.
• It is caused by mutations in CDK5RAP2.
• Phenotypes include reduced head circumference and other abnormalities, but not cataracts.

Purpose of the Study:

• To report a novel clinical manifestation in primary microcephaly type 3.
• To identify the genetic cause of microcephaly and congenital cataracts in a Saudi family.

Main Methods:

• Next-generation sequencing (NGS) gene panel for microcephaly.
• Sanger sequencing for segregation analysis.
• Autozygosity mapping and whole exome sequencing.

Main Results:

• Identified a CDK5RAP2 variant (c.4055A>G; p.Glu1352Gly) in affected family members.
• Congenital cataracts were observed in affected individuals, a previously unreported feature.
• Segregation analysis confirmed the variant as the likely cause.

Conclusions:

• Congenital cataracts are a newly identified clinical manifestation of primary microcephaly type 3.
• This expands the known phenotype associated with CDK5RAP2 mutations.
• The findings highlight genetic heterogeneity and the importance of comprehensive phenotyping.