Compound heterozygous CORO1A mutations in siblings with a mucocutaneous-immunodeficiency syndrome of epidermodysplasia verruciformis-HPV, molluscum contagiosum and granulomatous tuberculoid leprosy

J Clin Immunol. 2014 Oct;34(7):871-90. doi: 10.1007/s10875-014-0074-8. Epub 2014 Jul 30.


Purpose: Coronin-1A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO1A (OMIM 605000) that results in T-cell lymphopenia and is classified as T(-)B(+)NK(+)severe combined immunodeficiency (SCID). Only two other CORO1A-kindred are known to date, thus the defining characteristics are not well delineated. We identified a unique CORO1A-kindred.

Methods: We captured a 10-year analysis of the immune-clinical phenotypes in two affected siblings from disease debut of age 7 years. Target-specific genetic studies were pursued but unrevealing. Telomere lengths were also assessed. Whole exome sequencing (WES) uncovered the molecular diagnosis and Western blot validated findings.

Results: We found the compound heterozygous CORO1A variants: c.248_249delCT (p.P83RfsX10) and a novel mutation c.1077delC (p.Q360RfsX44) (NM_007074.3) in two affected non-consanguineous siblings that manifested as absent CD4CD45RA(+) (naïve) T and memory B cells, low NK cells and abnormally increased double-negative (DN) ϒδ T-cells. Distinguishing characteristics were late clinical debut with an unusual mucocutaneous syndrome of epidermodysplasia verruciformis-human papilloma virus (EV-HPV), molluscum contagiosum and oral-cutaneous herpetic ulcers; the older female sibling also had a disfiguring granulomatous tuberculoid leprosy. Both had bilateral bronchiectasis and the female died of EBV+ lymphomas at age 16 years. The younger surviving male, without malignancy, had reproducibly very short telomere lengths, not before appreciated in CORO1A mutations.

Conclusion: We reveal the third CORO1A-mutated kindred, with the immune phenotype of abnormal naïve CD4 and DN T-cells and newfound characteristics of a late/hypomorphic-like SCID of an EV-HPV mucocutaneous syndrome with also B and NK defects and shortened telomeres. Our findings contribute to the elucidation of the CORO1A-SCID-CID spectrum.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • B-Lymphocytes / physiology*
  • CD4-Positive T-Lymphocytes / physiology*
  • Child
  • DNA Mutational Analysis
  • Epidermodysplasia Verruciformis / etiology
  • Epidermodysplasia Verruciformis / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Granuloma / complications
  • Granuloma / genetics*
  • Heterozygote
  • Humans
  • Immunologic Memory / genetics
  • Killer Cells, Natural / physiology*
  • Leprosy, Tuberculoid / complications
  • Leprosy, Tuberculoid / genetics*
  • Male
  • Microfilament Proteins / genetics*
  • Molluscum Contagiosum / genetics*
  • Mucous Membrane / pathology*
  • Mucous Membrane / virology
  • Mutation / genetics
  • Papillomavirus Infections / etiology
  • Papillomavirus Infections / genetics*
  • Polymorphism, Genetic
  • Severe Combined Immunodeficiency / complications
  • Severe Combined Immunodeficiency / genetics*
  • Siblings
  • Skin / pathology*
  • Skin / virology
  • Telomere Shortening / genetics


  • Microfilament Proteins
  • coronin proteins