Identification of two molecular defects in a child with leukocyte adherence deficiency.

Back, Anthony L.; Kwok, William W.; Hickstein, Dennis D.

doi:10.1016/s0021-9258(18)42791-3

Cited by 50 publications

(2 citation statements)

References 36 publications

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“…A homozygous novel c.779_786dup mutation was identified in one patient; the CD18 expression in this patient was 1%. Homozygous c.382G>A, c.382G>T, c.533C>T, c.562C>T, c.817G>A and compound heterozygous c.1777C>T and c.533C>T mutations identified in seven patients in our cohort have been reported previously [18][19][20][21][22][23]. Large chromosomal deletions, including a whole ITGB2 gene deletion and exonic deletions, were reported in several studies [3,[23][24][25][26].…”

Section: Discussionsupporting

confidence: 75%

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey

Yaz

Özbek

Bildik

et al. 2021

Clinical and Experimental Immunology

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Leukocyte adhesion de ciency type I is rare primary immunode ciency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion de ciency type I (LAD-I). Targeted next-generation sequencing was performed with either a primary immunode ciency gene panel comprising 266 genes or a small LADpanel consisting of ve genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, ow cytometry analysis was performed. The median age of the patients at diagnosis was 3 (1-48) months. Eleven (73%) of the 15 patients had LAD-I diagnosis in their rst 6 months, and fourteen (93%) patients had consanguineous parents. Delayed separation of the umbilical cord was present in 80% (n=12) of the patients in our cohort, whereas omphalitis was observed in 53% (n=8) of the patients. Leukocytosis with neutrophil predominance was observed in 73% (n=11) patients. Nine distinct variants in the ITGB2 gene in 13 of the 15 patients with LAD-I were characterized, of which two (c.305_306delAA and c.779_786dup) are novel homozygous mutations of ITGB2 . Four unrelated patients from Syria had a novel c.305_306delAA mutation that might be a founder effect for patients of Syrian origin. Four (27%) patients underwent HSCT. Two of them died because of HSCT complications, and the other two are alive and well. Early differential diagnosis of the patients is critical in the management of the disease and genetic evaluation provides a basis for family studies and genetic counseling.

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Section: Discussionsupporting

confidence: 75%

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey

Yaz

Özbek

Bildik

et al. 2021

Clinical and Experimental Immunology

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“…Leukocyte adhesion deficiency 1 is a rare immunodeficiency due to a homozygous LOF mutation in ITGB2 gene, encoding the beta-2-integrin (CD18), which plays a key role in adhesion of neutrophils to the endothelium and their transmigration in tissues. The disease is characterized by recurrent bacterial infections, which start in infancy and affect the skin, the oral cavity and the respiratory tract [65]. Adult patients often present severe periodontitis, which can result in premature tooth loss.…”

Section: Autoimmune Lymphoproliferative Syndrome (Alps) Ormentioning

confidence: 99%

Repositioning Drugs for Rare Immune Diseases: Hopes and Challenges for a Precision Medicine

Valencic

Šmid

Tommasini

et al. 2018

CMC

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Human primary immunodeficiency diseases (PIDs) are a large group of rare diseases and are characterized by a great genetic and phenotypic heterogeneity. A large subset of PIDs is genetically defined, which has a crucial impact for the understanding of the molecular basis of disease and the development of precision medicine. Discovery and development of new therapies for rare diseases has long been de-privileged due to the length and cost of the processes involved. Interest has increased due to stimulatory regulatory and supportive reimbursement environments enabling viable business models. Advancements in biomedical and computational sciences enable the development of rational, designed approaches for identification of novel indications of already approved drugs allowing faster delivery of new medicines. Drug repositioning is based either on clinical analogies of diseases or on understanding of the molecular mode of drug action and mechanisms of the disease. All of these are the basis for the development of precision medicine.

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Chemotaxis of non‐compressed blood polymorphonuclear leukocytes from an adolescent with severe leukocyte adhesion deficiency

Malawista

Chevance²,

Brown

et al. 2003

American J Hematol

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We have defined the defect in a child with severe leukocyte adhesion deficiency-1 (LAD) as resulting from a single amino acid shift in CD18 (from a C to T mutation at position 533) that prevents heterodimerization with the CD11 antigens to produce ␤ 2 integrins-the first reported patient homozygous for this defect. Although beset by frequent infections, the patient has survived to adolescence despite the lack of these important adhesion

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Identification of two molecular defects in a child with leukocyte adherence deficiency.

Cited by 50 publications

References 36 publications

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey

Repositioning Drugs for Rare Immune Diseases: Hopes and Challenges for a Precision Medicine

Chemotaxis of non‐compressed blood polymorphonuclear leukocytes from an adolescent with severe leukocyte adhesion deficiency

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