This website provides information on patients with mutations in the POLD3 gene, including clinical data, molecular data, management and research options.

The syndrome caused by biallelic mutations in the POLD3 gene is a multisystem disorder characterized by severe primary immunodeficiency disease (T-cell deficiency / Severe Combined Immunodeficiency (SCID) to Omenn spectrum), developmental defects associated with neurodevelopmental delay with/without sensorineural hearing impairment.

These features reflect the essential role of the POLD3 accessory subunit in DNA replication and genome maintenance; defects lead to replication stress, impaired S-phase entry, and accumulation of DNA damage in patient cells.

To date, two reports of human cases with POLD3 deficiency have been described in the literature:
•    A consanguineous Lebanese family, with 4 affected individuals, presenting with syndromic severe combined immunodeficiency, neurodevelopmental delay and congenital hearing impairment.
•    A patient, issued from consanguineous parents of Moroccan descent, presenting with Omenn syndrome due to autosomal-recessive POLD3 deficiency; in whom functional studies showed defective S-phase entry and increased double-strand DNA break foci.

In addition, a recently described form demonstrates POLD3 haploinsufficiency as a cause for autosomal dominant, non-syndromic sensorineural adult-onset progressive hearing and balance impairments.

This website was created to share and collect information about clinic, management and research projects to gather more knowledge and provide better treatment of patients with mutations in the POLD3 gene.

Cybel Mehawej, PhD, Lebanese American University, Beirut, Lebanon, cybel.mehawej@lau.edu.lb

Andre Megarbane, MD, PhD, Lebanese American University, Beirut, Lebanon, andre.megarbane@lau.edu.lb

Eliane Chouery, PhD, Lebanese American University, Beirut, Lebanon, eliane.choueiry01@lau.edu.lb