A novel mutation of the ITGB2 gene in a Chinese Zhuang minority patient with leukocyte adhesion deficiency type 1 and glucose-6-phosphate dehydrogenase deficiency

Yu, Zhongxin; Yang, Xingliang; He, Xiaoli; Liu, Haifeng; Guo, Peng; Liu, Xiaoning; Xiao, Yang; Feng, Xingxing; Wang, Yanchun; Li, Li

doi:10.1016/j.gene.2019.144027

Cited by 7 publications

(4 citation statements)

References 40 publications

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“…Therefore, CD11/CD18 expression was considered as a marker for clinical diagnosis and disease severity of LAD-1 [19][20][21] and should be used as a first-line diagnostic approach in patients suspected to have LAD disease. Furthermore, the results of these initial immunophenotyping and functional assay tests could direct the geneticist to target quickly the responsible gene and give molecular confirmation to the clinicians to start therapeutic management.…”

Section: Discussionmentioning

confidence: 99%

Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1

Bouhouche

Tabache

Askander

et al. 2022

BioMed Research International

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Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin β2 subunit gene ITGB2, which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Sanger sequencing of all exons and intron boundaries of ITGB2 identified a novel in-frame deletion in exon 7 (ITGB2 c.844_846delAAC, p.Asn282del) in the patient. The p.Asn282del mutation was heterozygous in the child’s parents, whereas it was absent in the 96 control individuals from North Africa. This variant was evaluated by two in silico mutation analysis tools, PROVEAN and MutationTaster, which predicted that the mutation was likely to be pathogenic. In addition, molecular modeling with the YASARA View software suggested that this novel mutation may affect the structure of integrin beta-2 and, subsequently, its interaction with integrin alpha-X. In summary, we report a novel pathogenic mutation p.Asn282del associated with LAD1 that expands the mutation diversity of ITGB2 and suggest the combination of flow cytometry and ITGB2 sequencing as a first-line diagnostic approach for LAD disease.

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Section: Discussionmentioning

confidence: 99%

Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1

Bouhouche

Tabache

Askander

et al. 2022

BioMed Research International

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“…ITGB2 encodes integrin beta chain, a cell surface protein involved in cell adhesion and cell surface-mediated signal transduction. ITGB2 plays a significant role in the immune response, and ITGB2 deficiency causes leukocyte adhesion defects (45,46). A prospective study revealed that high ITGB2 expression in cancer-associated fibroblasts promoted tumor proliferation in oral squamous cell carcinoma through NADH oxidation in the mitochondrial oxidative phosphorylation system (47).…”

Section: Discussionmentioning

confidence: 99%

Identification of Genes Related to Immune Infiltration in the Tumor Microenvironment of Cutaneous Melanoma

et al. 2021

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Cutaneous melanoma (CM) is the leading cause of skin cancer deaths and is typically diagnosed at an advanced stage, resulting in a poor prognosis. The tumor microenvironment (TME) plays a significant role in tumorigenesis and CM progression, but the dynamic regulation of immune and stromal components is not yet fully understood. In the present study, we quantified the ratio between immune and stromal components and the proportion of tumor-infiltrating immune cells (TICs), based on the ESTIMATE and CIBERSORT computational methods, in 471 cases of skin CM (SKCM) obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were analyzed by univariate Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis to identify prognosis-related genes. The developed prognosis model contains ten genes, which are all vital for patient prognosis. The areas under the curve (AUC) values for the developed prognostic model at 1, 3, 5, and 10 years were 0.832, 0.831, 0.880, and 0.857 in the training dataset, respectively. The GSE54467 dataset was used as a validation set to determine the predictive ability of the prognostic signature. Protein–protein interaction (PPI) analysis and weighted gene co-expression network analysis (WGCNA) were used to verify “real” hub genes closely related to the TME. These hub genes were verified for differential expression by immunohistochemistry (IHC) analyses. In conclusion, this study might provide potential diagnostic and prognostic biomarkers for CM.

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“…After obtaining informed consent from the patient and her family, peripheral blood was sampled from the patient, her younger brother, and their parents. In order to better describe identification of the variant, we have added more detailed steps for genetic testing, data screening and pathogenicity analysis based on previous articles published after the company's WES technical services (Ma et al, 2019;Zhang et al, 2019). We isolated nucleic acid to capture DNA fragments, then constructed a library, using biotinylated probes to target and capture exons, and amplify the captured targets, qPCR was used for quality control and sequencing, and to analyze the captured information.…”

Section: Case Reportmentioning

confidence: 99%

“…Her parent's and younger brother's samples were tested via Sanger sequencing for verification (Supplementary Figure S1). With pathogenicity analysis (Zhang et al, 2019), we detected the pathogenic locus (Supplementary Figure S2). The patient's DCAF17 harbored a homozygous mutation c.1111delA, p.(Ile371Term), her younger brother had the same mutation, and her parents were heterozygous for the mutation at this site.…”

Section: Case Reportmentioning

confidence: 99%

Case Report: A Deletion Variant in the DCAF17 Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family

et al. 2021

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Woodhouse-Sakati syndrome (WSS, MIM 241080) is a rare neuroendocrine disease characterized by hair loss, hypogonadism, diabetes, hearing loss, and extrapyramidal syndrome, and is usually caused by mutations in the DCAF17 gene as an inherited disease. DCAF17 plays an important role in mammalian gonadal development and infertility. So far, there have been no WSS reports in China. The patient introduced in this case is from a consanguineous family. The main symptoms of the patient were alopecia and gonadal agenesis. Other symptoms such as hearing loss, intellectual disability, and hyperglycemia were remarkable, and these symptoms are often observed in WSS patients. We found a nonsense mutation in the 11th exon of the gene DCAF17 (Refseq: NM_025000) in the patient and her younger brother, which confirmed the diagnosis of WSS. The genetic results also showed that the mutation was inherited from their healthy first-cousin parents.

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A novel mutation of the ITGB2 gene in a Chinese Zhuang minority patient with leukocyte adhesion deficiency type 1 and glucose-6-phosphate dehydrogenase deficiency

Cited by 7 publications

References 40 publications

Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1

Novel ITGB2 Mutation Is Responsible for a Severe Form of Leucocyte Adhesion Deficiency Type 1

Identification of Genes Related to Immune Infiltration in the Tumor Microenvironment of Cutaneous Melanoma

Case Report: A Deletion Variant in the DCAF17 Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family

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