LIG4 Syndrome Presenting with Extensive Cutaneous Viral Warts Caused by Multi-Type HPV Infection.

Background

DNA Ligase 4 (LIG4) catalyzes the final ligation step during V(D)J recombination. Biallelic pathogenic variants in LIG4 cause severe combined immunodeficiency (SCID), a life-threatening immunodeficiency characterized by the lack of mature T and B cells. Case Presentation: An 18-year-old male exhibited widespread verrucous and keratotic cutaneous lesions across the face, neck, and extremities. The proband manifested early-onset short stature, chronic malnutrition, recurrent pulmonary infections with bronchiectasis, chronic diarrhea, and bilateral tenosynovitis. Immunophenotyping revealed persistent panhypogammaglobulinemia, absent B cells, reduced T and natural killer (NK) cells, and nearly undetectable naïve T cells. Both α-HPV and β-HPV were detected in the cutaneous lesions. Compound heterozygous LIG4 variants (hg19, NM206937.2, c.833G > T; p.Arg278Leu inherited from the mother; c.833G > A; p.Arg278 His inherited from the father) were identified.

Conclusions

This study reports a proband with LIG4 syndrome presenting with rare phenotypes of multiple viral warts and combined lymphopenia of T, B, and NK cells. This proband harbors compound heterozygous variants at the same codon (c.833G), which not only confirm the clinical diagnosis but also enrich the known phenotypic spectrum of LIG4 syndrome.