A novel 3′ splice-site mutation and a novel gross deletion in leukocyte adhesion deficiency (LAD)-1

Cher, T.H. Bernard; Chan, H. S. O.; Klein, Georg; Jabkowski, Jörg; Schadenböck-Kranzl, Gabriela; Zach, Otto; Roca, Xavier; Law, S.K. Alex

doi:10.1016/j.bbrc.2010.12.124

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…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 identi ed in 7 patients in our cohort were reported previously [15][16][17][18][19][20]. Large chromosomal deletions, including a whole ITGB2 gene deletion and exonic deletions, were reported in several studies [3,[20][21][22][23]. In our cohort, one patient harbored a large deletion (exon 12_14), which is probably the same as one reported previously [3].…”

Section: Discussionsupporting

confidence: 73%

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: 73%

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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Section: Discussionsupporting

confidence: 71%

Clinical and Laboratory Findings in Patients with Leukocyte Adhesion Deficiency Type I: A Multicenter Study in Turkey

Yaz

Özbek

Bildik

et al. 2021

Preprint

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Leukocyte adhesion deficiency type I is rare primary immunodeficiency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion deficiency type I (LAD-I). Targeted next-generation sequencing was performed with either a primary immunodeficiency gene panel comprising 266 genes or a small LAD-panel consisting of five genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, flow 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 first 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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“…In fact, Cher et al has shown by RT‐PCR that this variant change has resulted in an alternative transcript with an insertion of 43 bp intronic sequence that leads to premature termination. This variant has been reported previously in an LAD‐I patient and shown to result in a premature stop codon (p.C19_V20ins11X12) 25 …”

Section: Case Presentationsupporting

confidence: 58%

“…This variant has been reported previously in an LAD-I patient and shown to result in a premature stop codon (p.C19_V20ins11X12). 25 At the moment of diagnosis at the age of 2 years and further with a re-examination at 14 years, CD18 expression on PMN was 1% and 1.5%, correspondently, which is consistent with severe LAD-1. However, the clinical picture did not match these results, such low expression would lead to more severe and frequent infectious episodes.…”

Section: Laboratory Findings (Genetic Testing and Cd18 Expression Stu...supporting

confidence: 53%

Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

Bondarenko,

Boyarchuk,

Sakovich

et al. 2023

Clinical Case Reports

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Key Clinical MessagePartial leukocyte adhesion deficiency type 1 (LAD‐1) deficiency is extremely rare condition with milder infectious manifestation and immune system imbalance leads to increased risks of autoinflammatory complications, such as pyoderma gangrenosum, that can be triggered by trauma or pregnancy. In patients with spice‐site ITGB2 variants, partial expression can occur due to different β2 integrin isophorms expression.AbstractLAD‐1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 β2 integrin subunit. According to the CD18 expression, LAD‐1 is categorized as severe (<2%), moderate (2%–30%), or mild (>30%). Here, we describe a 22‐year‐old female, who presented with inflammatory skin disease and oral cavity, as well as respiratory tract infections during the first year of life. LAD‐1 was diagnosed at the age of 2 years by low expression of CD18 (1%). Whole‐exome sequencing identified homozygous c. 59‐10C>A variant in the ITGB2 gene. Despite severe phenotype, the patient survived to adulthood without hematopoietic stem cell transplantation and became pregnant at the age of 20 years, with pregnancy complicated by a pyoderma gangrenosum‐like lesion. During her life, CD18 expression increased from 1% to 9%; at 22 years of age, 5% of neutrophils and 9% of lymphocytes were CD18+. All CD18+‐lymphocytes were predominantly memory/effector cytotoxic T cells. However, revertant mosaicism was not being established suggesting that CD18 expression variability may be mediated by other mechanisms such as different β2 integrin isophorms expression.

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A novel 3′ splice-site mutation and a novel gross deletion in leukocyte adhesion deficiency (LAD)-1

Cited by 11 publications

References 28 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

Clinical and Laboratory Findings in Patients with Leukocyte Adhesion Deficiency Type I: A Multicenter Study in Turkey

Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

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