title: Inherited MST1 deficiency underlies susceptibility to EV-HPV infections.
abstract: Epidermodysplasia verruciformis (EV) is characterized by persistent cutaneous lesions caused by a specific group of related human papillomavirus genotypes (EV-HPVs) in otherwise healthy individuals. Autosomal recessive (AR) EVER1 and EVER2 deficiencies account for two thirds of known cases of EV. AR RHOH deficiency has recently been described in two siblings with EV-HPV infections as well as other infectious and tumoral manifestations. We report here the whole-exome based discovery of AR MST1 deficiency in a 19-year-old patient with a T-cell deficiency associated with EV-HPV, bacterial and fungal infections. MST1 deficiency has recently been described in seven patients from three unrelated kindreds with profound T-cell deficiency and various viral and bacterial infections. The patient was also homozygous for a rare ERCC3 variation. Our findings broaden the clinical range of infections seen in MST1 deficiency and provide a new genetic etiology of susceptibility to EV-HPV infections. Together with the recent discovery of RHOH deficiency, they suggest that T cells are involved in the control of EV-HPVs, at least in some individuals.
authors.affiliation: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.
authors.forename: Amandine
authors.initials: A
authors.lastname: Crequer
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Etienne
authors.initials: E
authors.lastname: Patin
authors.forename: Aurelia
authors.initials: A
authors.lastname: D'Amico
authors.forename: Avinash
authors.initials: A
authors.lastname: Abhyankar
authors.forename: Martine
authors.initials: M
authors.lastname: Munzer
authors.forename: Marianne
authors.initials: M
authors.lastname: Debré
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Geneviève
authors.initials: G
authors.lastname: de Saint-Basile
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Gérard
authors.initials: G
authors.lastname: Orth
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jouanguy
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics; D004819:Epidermodysplasia Verruciformis / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000821:virology; D059472:Exome / Q000235:genetics; D020022:Genetic Predisposition to Disease; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D027383:Papillomaviridae / Q000187:drug effects / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D018389:Codon, Nonsense; D008934:Mitogens; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor