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

[severe combined immunodeficiency]

Coronin-1 A deficiency is a recently recognized autosomal recessive primary immunodeficiency caused by mutations in CORO 1 A (OMIM 605000 ) that results in T -cell lymphopenia and is classified as T (-)B (+)NK (+)severe combined immunodeficiency (SCID ). Only two other CORO 1 A -kindred are known to date , thus the defining characteristics are not well delineated . We identified a unique CORO 1 A -kindred .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 .We found the compound heterozygous CORO 1 A variants : c .248 _249 delCT (p .P 83 RfsX 10 ) and a novel mutation c .1077 delC (p .Q 360 RfsX 44 ) (NM _007074 .3 ) in two affected non-consanguineous siblings that manifested as absent CD 4 CD 4 5 RA (+) (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 CORO 1 A mutations .We reveal the third CORO 1 A -mutated kindred , with the immune phenotype of abnormal naïve CD 4 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 CORO 1 A -SCID -CID spectrum .