Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency

Assiya El Kettani; Hind Ouair; Farida Marnissi; Jalila El Bakkouri; Rémi Chevalier; Lazaro Lorenzo; Halima Kholaiq; Vivien Béziat; Emmanuelle Jouanguy; Jean-Laurent Casanova; Ahmed Aziz Bousfiha

doi:10.3390/v16091415

Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency

Viruses. 2024 Sep 5;16(9):1415. doi: 10.3390/v16091415.

Authors

Assiya El Kettani^{1

2

3}, Hind Ouair³, Farida Marnissi⁴, Jalila El Bakkouri^{1

5}, Rémi Chevalier^{6

7}, Lazaro Lorenzo^{6

7}, Halima Kholaiq¹, Vivien Béziat^{6

7

8}, Emmanuelle Jouanguy^{6

7

8}, Jean-Laurent Casanova^{6

7

8

9}, Ahmed Aziz Bousfiha^{1

10}

Affiliations

¹ Laboratory of Clinical Immunology-Inflammation and Allergy (LICIA), Faculty of Medicine and Pharmacy, Hassan II University, Casablanca 20250, Morocco.
² Laboratory of Bacteriology, Virology and Hospital Hygiene, Ibn Rochd University Hospital, Casablanca 20250, Morocco.
³ Laboratory of Bacteriology and Virology, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca 20250, Morocco.
⁴ Laboratory of Pathological Anatomy, Ibn Rochd University Hospital, Hassan II University, Casablanca 20250, Morocco.
⁵ Immunology Laboratory, Ibn Rochd University Hospital, Casablanca 20250, Morocco.
⁶ Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM), 75015 Paris, France.
⁷ Imagine Institute, Paris Cité University, 75015 Paris, France.
⁸ Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY 10065, USA.
⁹ Howard Hughes Medical Institute, Chevy Chase, MD 20815-6789, USA.
¹⁰ Clinical Immunology and Infectious Pediatrics Department, Abderrahim Harouchi Hospital-Ibn Rochd University Hospital, Casablanca 20250, Morocco.

Abstract

Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by β-human papillomaviruses (HPV) in immunodeficient patients. EV is characterized by flat warts and pityriasis-like lesions and might be isolated or syndromic, associated with some other infectious manifestations. We report here three patients from two independent families, with syndromic EV for both of them. By whole exome sequencing, we found that the patients carry new homozygous variants in STK4, both leading to a premature stop codon. STK4 deficiency causes a combined immunodeficiency characterized by a broad infectious susceptibility to bacteria, viruses, and fungi. Auto-immune manifestations were also reported. Deep immunophenotyping revealed multiple cytopenia in the three affected patients, in particular deep CD4⁺ T cells deficiency. We report here the fourth and the fifth cases of the syndromic EV due to STK4 deficiency.

Keywords: CD4+ T cells; STK4 deficiency; epidermodysplasia verruciformis; human papillomavirus.

Publication types

Case Reports

MeSH terms

Child
Child, Preschool
Epidermodysplasia Verruciformis* / genetics
Epidermodysplasia Verruciformis* / pathology
Epidermodysplasia Verruciformis* / virology
Exome Sequencing
Female
Humans
Intracellular Signaling Peptides and Proteins* / deficiency
Intracellular Signaling Peptides and Proteins* / genetics
Male
Morocco
Mutation
Pedigree
Protein Serine-Threonine Kinases* / deficiency
Protein Serine-Threonine Kinases* / genetics

Substances

STK4 protein, human
Protein Serine-Threonine Kinases
Intracellular Signaling Peptides and Proteins

Grants and funding

This work was founded by Laboratory of Clinical Immunology—Inflammation and Allergy (LICIA), Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco and The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI143810), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1TR001866), the program “Investissement d’Avenir” launched by the French Government and implemented by the Agence Nationale de la Recherche (ANR) (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the Square Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris Cité. T.L.V. is funded by the MD-PhD program of Imagine Institute.