Molecular characteristics

Gene:POLA1(DNA polymerase alpha catalytic subunit)
Inheritance: X-linked recessive

Mutation spectrum
•    Hemizygous pathogenic variants in POLA1 identified in affected males
•    Multiple distinct mutations reported across unrelated families

Mechanism (current understanding)
•    Reduced or altered function of DNA polymerase-α
•    Likely effects on DNA replication and cell proliferation pathways

(Mechanistic detail remains incompletely defined; literature emphas phenotype rather than pathway specificity.)

Diagnostic testing
•    Sequencing of POLA1(exome or gene panel)
•    Deletion/duplication analysis if needed