Publications by authors named "Eman AlIdrissi"

3 Publications

  • Page 1 of 1

Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies.

Genome Med 2019 06 17;11(1):38. Epub 2019 Jun 17.

Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: Diagnosis of primary immunodeficiencies (PIDs) is complex and cumbersome yet important for the clinical management of the disease. Exome sequencing may provide a genetic diagnosis in a significant number of patients in a single genetic test.

Methods: In May 2013, we implemented exome sequencing in routine diagnostics for patients suffering from PIDs. This study reports the clinical utility and diagnostic yield for a heterogeneous group of 254 consecutively referred PID patients from 249 families. For the majority of patients, the clinical diagnosis was based on clinical criteria including rare and/or unusual severe bacterial, viral, or fungal infections, sometimes accompanied by autoimmune manifestations. Functional immune defects were interpreted in the context of aberrant immune cell populations, aberrant antibody levels, or combinations of these factors.

Results: For 62 patients (24%), exome sequencing identified pathogenic variants in well-established PID genes. An exome-wide analysis diagnosed 10 additional patients (4%), providing diagnoses for 72 patients (28%) from 68 families altogether. The genetic diagnosis directly indicated novel treatment options for 25 patients that received a diagnosis (34%).

Conclusion: Exome sequencing as a first-tier test for PIDs granted a diagnosis for 28% of patients. Importantly, molecularly defined diagnoses indicated altered therapeutic options in 34% of cases. In addition, exome sequencing harbors advantages over gene panels as a truly generic test for all genetic diseases, including in silico extension of existing gene lists and re-analysis of existing data.
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http://dx.doi.org/10.1186/s13073-019-0649-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572765PMC
June 2019

Three Types of Immunodeficiency, Centromeric Instability, and Facial Anomalies (ICF) Syndrome Identified by Whole-Exome Sequencing in Saudi Hypogammaglobulinemia Patients: Clinical, Molecular, and Cytogenetic Features.

J Clin Immunol 2018 11 3;38(8):847-853. Epub 2018 Dec 3.

Allergy and Immunology Section, Children's Specialized Hospital, King Fahad Medical City, Makkah Almukaramah Road, As Sulimaniyah 6481, Riyadh, 12231, Saudi Arabia.

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http://dx.doi.org/10.1007/s10875-018-0569-9DOI Listing
November 2018

Biallelic mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.

Science 2018 08 19;361(6404):810-813. Epub 2018 Jul 19.

Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.

RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.
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http://dx.doi.org/10.1126/science.aar2641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529353PMC
August 2018