ArticleJournal of clinical immunology2015
Whole Genome Sequencing Reveals a Chromosome 9p Deletion Causing DOCK8 Deficiency in an Adult Diagnosed with Hyper IgE Syndrome Who Developed Progressive Multifocal Leukoencephalopathy.
Article in Journal of clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Genetic mechanisms underlying host susceptibility to central nervous system viral infections.Current opinion in infectious diseases · 2026Review
- Progressive multifocal leukoencephalopathy in a young adult with DOCK8 deficiency: a case of JC virus reactivation in primary immunodeficiency.Journal of neurovirology · 2025Article
- Hyper IgE Syndromes: Understanding, Management, and Future Perspectives: A Narrative Review.Health science reports · 2025Article
- Genetics of progressive multifocal leukoencephalopathy: update on case reports with an inborn error of immunity and risk variants found in drug-linked cases.Frontiers in neurology · 2025Review
- Using a new analytic approach for genotyping and phenotyping chromosome 9p deletion syndrome.European journal of human genetics : EJHG · 2024Article
- Progressive multifocal leukoencephalopathy in a patient with novel mutation in the RAC2 gene: a case report.Journal of medical case reports · 2022Article
- Progressive multifocal leukoencephalopathy genetic risk variants for pharmacovigilance of immunosuppressant therapies.Frontiers in neurology · 2022Article
- Immunity and Genetics at the Revolving Doors of Diagnostics in Primary Immunodeficiencies.Diagnostics (Basel, Switzerland) · 2021Article
- Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy.Frontiers in neurology · 2020Article
- DOCK8 deficiency: Insights into pathophysiology, clinical features and management.Clinical immunology (Orlando, Fla.) · 2017Review
- Progressive multi-focal leucoencephalopathy - driven from rarity to clinical mainstream by iatrogenic immunodeficiency.Clinical and experimental immunology · 2017Review
- Homozygous and hemizygous CNV detection from exome sequencing data in a Mendelian disease cohort.Nucleic acids research · 2017Article
- Whole genome sequencing of one complex pedigree illustrates challenges with genomic medicine.BMC medical genomics · 2017Article
- Progressive Multifocal Leukoencephalopathy in Primary Immune Deficiencies: Stat1 Gain of Function and Review of the Literature.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Review
- Broadly neutralizing human monoclonal JC polyomavirus VP1-specific antibodies as candidate therapeutics for progressive multifocal leukoencephalopathy.Science translational medicine · 2015Article
- Is there a (host) genetic predisposition to progressive multifocal leukoencephalopathy?Frontiers in immunology · 2015Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeA 30 year-old man with a history of recurrent skin infections as well as elevated serum IgE and eosinophils developed neurological symptoms and had T2-hyperintense lesions observed in cerebral MRI. The immune symptoms were attributed to Hyper IgE syndrome (HIES) and the neurological symptoms with presence of JC virus in cerebrospinal fluid were diagnosed as Progressive Multifocal Leukoencephalopathy (PML). The patient was negative for STAT3 mutations. To determine if other mutations explain HIES and/or PML in this subject, his DNA was analyzed by whole genome sequencing.
methodsWhole genome sequencing was completed to 30X coverage, and whole genome SNP typing was used to complement these data. The methods revealed single nucleotide variants, structural variants, and copy number variants across the genome. Genome-wide data were analyzed for homozygous or compound heterozygous null mutations for all protein coding genes. Mutations were confirmed by PCR and/or Sanger sequencing.
resultsWhole genome analysis revealed deletions near the telomere of both copies of chromosome 9p. Several genes, including DOCK8, were impacted by the deletions but it was unclear whether each chromosome had identical or distinct deletions. PCR across the impacted region combined with Sanger sequencing of selected fragments confirmed a homozygous deletion from position 10,211 to 586,751.
conclusionWhile several genes are impacted by the deletion, DOCK8 deficiency is the most probable cause of HIES in this patient. DOCK8 deficiency may have also predisposed the patient to develop PML.
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