• Recurrent POLA1deep intronic variant, NM_016937.3:c.1375-354A>G, creating an aberrant splice donor site resulting in tissue-specific partial missplicing of the POLA1transcript (hypomorphic or partial loss of function variant)
Pathophysiology
• Reduced POLA1expression
• Decreased cytosolic RNA:DNA hybrid resulting in aberrant activation of type I interferon pathways (mechanism unclear)
• Deficient NK cell number/activity contributing to immunodeficiency in some cases
Diagnostic testing
• Molecular genetic testing for causal variant by targeted PCR/DNA sequencing
• May also be identified by whole genome sequencing
• Offered as part of Autoinflammatory Disorders Gene Panel (Mayo Clinic AUTOG)
POLA1 XLPDR