title: Novel mutation in DOCK8-HIES with severe phenotype and successful transplantation.
abstract: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal recessive (AR) primary combined immunodeficiency which results in significant morbidity and mortality at a young age. Different mutations in the DOCK8 gene can lead to variable severity of the disease.
  
  
  
  We evaluated the genetic mutations in three related patients with severe clinical manifestations suggestive of AR HIES. We also explored whether treatment with stem cell transplantation could lead to complete disease resolution.
  
  
  
  We examined the clinical manifestations and immunological workup of these patients. Their DNA was also screened for causative mutation. Post transplantation, clinical and immunological data for the transplanted patient was also collected.
  
  
  
  All patients had a severe course of the disease with rarely reported severe complications in HIES. One patient died with lymphoma while another died with progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our patients had two novel mutations in the DOCK8 gene. One of these mutations was a novel pathogenic mutation and explains the severity of the disease (homozygous splice site mutation at position 5 after the end of exon 45), while the other mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation (HSCT) was performed in the youngest patient with excellent engraftment and full reversibility of the clinical manifestations.
  
  
  
  We report 3 patients from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete resolution of the clinical and immunological features in the third patient by HSCT.
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Medicine, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 46, Saudi Arabia. Electronic address: latifaalshukeili@hotmail.com.
authors.forename: Latifa
authors.initials: L
authors.lastname: Al Shekaili
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Medicine, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 46, Saudi Arabia. Electronic address: fsheikh96@kfshrc.edu.sa.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Sheikh
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Medicine, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 46, Saudi Arabia. Electronic address: gazlan@kfshrc.edu.sa.
authors.forename: Sulaiman
authors.initials: S
authors.lastname: Al Gazlan
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Pediatric, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 58, Saudi Arabia. Electronic address: haldhekri@kfshrc.edu.sa.
authors.forename: Hasan
authors.initials: H
authors.lastname: Al Dhekri
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Pediatric, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 58, Saudi Arabia. Electronic address: hamoudalmousa@kfshrc.edu.sa.
authors.forename: Hamoud
authors.initials: H
authors.lastname: Al Mousa
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Pediatric, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 58, Saudi Arabia. Electronic address: ghonaium@kfshrc.edu.sa.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Al Ghonaium
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Pediatric, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 58, Saudi Arabia. Electronic address: balsaud@kfshrc.edu.sa.
authors.forename: Bander
authors.initials: B
authors.lastname: Al Saud
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Pediatric, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 58, Saudi Arabia. Electronic address: smohsen@kfshrc.edu.sa.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al Mohsen
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Medicine, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 46, Saudi Arabia; Alfaisal University, Saudi Arabia. Electronic address: rehankhaliq@kfshrc.edu.sa.
authors.forename: Agha M
authors.initials: AM
authors.lastname: Rehan Khaliq
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Medicine, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 46, Saudi Arabia. Electronic address: ssumayli@kfshrc.edu.sa.
authors.forename: Safiah
authors.initials: S
authors.lastname: Al Sumayli
authors.affiliation: King Fahad medical city, Department of Medicine, Riyadh 11525, P.O. Box 59046, Saudi Arabia. Electronic address: rarnaut@kfshrc.edu.sa.
authors.forename: Mufarreh
authors.initials: M
authors.lastname: Al Zahrani
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Pathology and Lab Medicine, P.O Box 3354, Riyadh 11211, MBC 10, Saudi Arabia. Electronic address: mdababo@kfshrc.edu.sa.
authors.forename: Anas
authors.initials: A
authors.lastname: Dababo
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Neuroscience, P.O Box 3354, Riyadh 11211, MBC 76, Saudi Arabia. Electronic address: aalkawi@kfshrc.edu.sa.
authors.forename: Ammar
authors.initials: A
authors.lastname: AlKawi
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of genetics, P.O Box 3354, Riyadh 11211, MBC 3, Saudi Arabia. Electronic address: ahawwari@kfshrc.edu.sa.
authors.forename: Abbas
authors.initials: A
authors.lastname: Hawwari
authors.affiliation: King Faisal Specialist Hospital and Research Center, Department of Medicine, Allergy and Immunology section, P.O Box 3354, Riyadh 11211, MBC 46, Saudi Arabia; Alfaisal University, Saudi Arabia. Electronic address: rarnaout@kfshrc.edu.sa.
authors.forename: Rand
authors.initials: R
authors.lastname: Arnaout
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000209:etiology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D015209:Cholangitis, Sclerosing / Q000209:etiology; D003241:Consanguinity; D004485:Eczema / Q000209:etiology; D004802:Eosinophilia / Q000209:etiology; D020031:Epstein-Barr Virus Infections / Q000209:etiology; D004941:Esophagitis / Q000209:etiology; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006561:Herpes Simplex / Q000209:etiology; D006801:Humans; D007589:Job Syndrome / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D007889:Leiomyoma / Q000209:etiology / Q000821:virology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000821:virology; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense; D009303:Nasopharyngeal Neoplasms / Q000209:etiology / Q000821:virology; D010375:Pedigree; D012008:Recurrence; D013203:Staphylococcal Infections / Q000209:etiology; D055815:Young Adult
chemical_list: C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors
keywords: Adrenal Epstein–Barr virus (EBV)-related Leiomyoma; DOCK8 deficiency; Hyper-IgE syndrome; Novel mutations; Progressive multifocal leukoencephalopathy; Slow virus