Is Your Kid Actin Out? A Series of Six Patients With Inherited Actin-Related Protein 2/3 Complex Subunit 1B Deficiency and Review of the Literature.

Gustavo Varela-Fascinetto, Saul Oswaldo Lugo Reyes, Bertrand Boisson, Gabriel López-Velázquez, Aidé Tamara Staines Boone, Sara Elva Espinosa-Padilla, Jean-Laurent Casanova, César Mauricio Rojas Maruri, Noemí Gómez Hernández, Ezequiel Moisés Fuentes-Pananá, Laura Cecilia Bonifaz Alonzo, Yuridia Salazar Gálvez, Rosa María Nideshda Ramírez-Uribe, Estefanía Vásquez-Echeverri, Alejandra Consuelo Sanchez, Pedro Francisco Valencia Mayoral, Margarita Ortega Cisneros, María Guadalupe González-Villarreal, Juan Carlos Bustamante Ogando, Melissa Espinosa-Navarro, Maria Edith González-Serrano, Edgar Alejandro Medina-Torres, Lina Maria Castano-Jaramillo, Selma Cecilia Scheffler Mendoza, Edna Venegas Montoya, Marco Antonio Yamazaki-Nakashimada

Journal: The journal of allergy and clinical immunology. In practice 2023;11(4):1261-1280.e8

PMID: 36708766

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Abstract

BACKGROUND

Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy.

OBJECTIVE

We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families.

METHODS

We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency.

RESULTS

Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells.

CONCLUSION

Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.

Address: Immune Deficiencies Laboratory, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico.; Clinical Immunology Service, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico.; Immunology Service, Unidad Médica de Alta Especialidad, Monterrey, Nuevo Leon, Mexico.; Clinical Immunology Service, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico; Fundación Hospital de la Misericordia, Bogotá, Colombia.; Hematology Service, Unidad Médica de Alta Especialidad, Monterrey, Nuevo Leon, Mexico.; Allergy and Clinical Immunology Service, Unidad Médica de Alta Especialidad, Centro Médico Nacional de Occidente IMSS, Guadalajara, Jalisco, Mexico.; Pathology Department, Hospital Infantil de Mexico "Dr Federico Gomez," Mexico City, Mexico.; Pediatric Gastroenterology and Nutrition Department, Hospital Infantil de Mexico "Dr Federico Gomez," Mexico City, Mexico.; Transplantation Department, Hospital Infantil de Mexico "Dr Federico Gomez," Mexico City, Mexico.; Stem Cell Transplantation Unit, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico.; Immunochemistry Research Unit, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico.; Research Unit on Virology and Cancer, Hospital Infantil de Mexico "Dr Federico Gomez," Mexico City, Mexico.; Pathology Department, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico.; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York City, NY; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France; Imagine Institute, University of Paris, Paris, France; Department of Pediatrics, Necker Hospital for Sick Children, Paris, France; Howard Hughes Medical Institute, Paris, France.; Immune Deficiencies Laboratory, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico. Electronic address: [email protected].; Immunology Service, Unidad Médica de Alta Especialidad, Monterrey, Nuevo Leon, Mexico. Electronic address: [email protected].; Laboratory of Biomolecules and Infant Health, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico.; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York City, NY; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France; Imagine Institute, University of Paris, Paris, France.; Immune Deficiencies Laboratory, National Institute of Pediatrics, Health Secretariat, Mexico City, Mexico. Electronic address: [email protected].

DOI: 10.1016/j.jaip.2022.12.045

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MeSH Terms: Humans, Actin-Related Protein 2, Actins, Eczema, Eosinophilia, Epstein-Barr Virus Infections, Failure to Thrive, Herpesvirus 4, Human, Immunoglobulin A, Immunoglobulin E, Reinfection, Vasculitis, Actin-Related Protein 3