Successful hematopoietic stem cell transplant in leukocyte adhesion deficiency type III presenting primarily as malignant infantile osteopetrosis

Essa, Mohammed Al; Elbashir, Enas; Alroqi, Fayhan; Mohammed, Reem; Alsultan, Abdulrahman

doi:10.1016/j.clim.2020.108365

Cited by 11 publications

(9 citation statements)

References 19 publications

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“…6-9 in Table 1 and Figure 1) (43). The deficiency of the b2 integrin subunit of the LFA-1 causes the leukocyte adhesion deficiency (LAD) type I, and the defective activation of LFA-1 subunits has been related to the LAD type III, both nowadays effectively treated with the hematopoietic stem cells transplantation (44,45). On the other side, LAD type II is caused by mutations of a fucose transporter gene leading to cell membrane glycans lacking fucosylation.…”

Section: Activation Defectsmentioning

confidence: 99%

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

et al. 2021

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A growing number of monogenic immune-mediated diseases have been related to genes involved in pathways of actin cytoskeleton remodeling. Increasing evidences associate cytoskeleton defects to autoinflammatory diseases and primary immunodeficiencies. We reviewed the pathways of actin cytoskeleton remodeling in order to identify inflammatory and immunological manifestations associated to pathological variants. We list more than twenty monogenic diseases, ranging from pure autoinflammatory conditions as familial Mediterranean fever, mevalonate kinase deficiency and PAPA syndrome, to classic and novel primary immunodeficiencies as Wiskott-Aldrich syndrome and DOCK8 deficiency, characterized by the presence of concomitant inflammatory and autoimmune manifestations, such as vasculitis and cytopenia, to severe and recurrent infections. We classify these disorders according to the role of the mutant gene in actin cytoskeleton remodeling, and in particular as disorders of transcription, elongation, branching and activation of actin. This expanding field of rare immune disorders offers a new perspective to all immunologists to better understand the physiological and pathological role of actin cytoskeleton in cells of innate and adaptive immunity.

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Section: Activation Defectsmentioning

confidence: 99%

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

et al. 2021

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“…The variant screening process was based on disease-related information and variant pathogenicity evaluation (allele frequency in population, in silico tools, ACMG guidelines) ( 23 , 24 ). Genetic disorders that frequently manifest phenotypes similar to our case include juvenile-myelomonocytic-leukemia (JMML) ( 5 , 17 , 25 ) and leukocyte adhesion deficiency (LAD) ( 1 , 26 , 27 ). JMML-related genes include PTPN11 , NRAS , KRAS , NF1 , and CBL .…”

Section: Methodsmentioning

confidence: 54%

A novel compound heterozygous mutation of the CLCN7 gene is associated with autosomal recessive osteopetrosis

Wang

et al. 2023

Front. Pediatr.

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Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability. Whole-exome sequencing (WES) followed by Sanger sequencing revealed novel compound heterozygous mutations in the chloride channel 7 (CLCN7) gene [c.982-1G > C and c.1208G > A (p. Arg403Gln)] in the affected individual, and subsequent familial segregation showed that each parent had transmitted a mutation. Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene and enhanced the applications of WES technology in determining the etiology of prenatal diagnoses in fetuses with ultrasound anomalies.

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“…Specifically, FERMT3 has been widely recognized for its role in cell adhesion, migration, and thrombosis. Several studies have demonstrated that mutations in FERMT3 can lead to leukocyte adhesion deficiency syndrome type 3 (LAD3), resulting in defective platelet function and immunodeficiency [26][27][28]. These findings suggest a potential regulatory role of FERMT3 in the interplay between inflammation and coagulation during the progression of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Immune-Related Molecules CD3G and FERMT3: Novel Biomarkers Associated with Sepsis

Li,

Ren,

Wang

et al. 2024

IJMS

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Sepsis ranks among the most common health problems worldwide, characterized by organ dysfunction resulting from infection. Excessive inflammatory responses, cytokine storms, and immune-induced microthrombosis are pivotal factors influencing the progression of sepsis. Our objective was to identify novel immune-related hub genes for sepsis through bioinformatic analysis, subsequently validating their specificity and potential as diagnostic and prognostic biomarkers in an animal experiment involving a sepsis mice model. Gene expression profiles of healthy controls and patients with sepsis were obtained from the Gene Expression Omnibus (GEO) and analysis of differentially expressed genes (DEGs) was conducted. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to analyze genes within crucial modules. The functional annotated DEGs which related to the immune signal pathways were used for constructing protein–protein interaction (PPI) analysis. Following this, two hub genes, FERMT3 and CD3G, were identified through correlation analyses associated with sequential organ failure assessment (SOFA) scores. These two hub genes were associated with cell adhesion, migration, thrombosis, and T-cell activation. Furthermore, immune infiltration analysis was conducted to investigate the inflammation microenvironment influenced by the hub genes. The efficacy and specificity of the two hub genes were validated through a mice sepsis model study. Concurrently, we observed a significant negative correlation between the expression of CD3G and IL-1β and GRO/KC. These findings suggest that these two genes probably play important roles in the pathogenesis and progression of sepsis, presenting the potential to serve as more stable biomarkers for sepsis diagnosis and prognosis, deserving further study.

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Successful hematopoietic stem cell transplant in leukocyte adhesion deficiency type III presenting primarily as malignant infantile osteopetrosis

Cited by 11 publications

References 19 publications

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

A novel compound heterozygous mutation of the CLCN7 gene is associated with autosomal recessive osteopetrosis

Immune-Related Molecules CD3G and FERMT3: Novel Biomarkers Associated with Sepsis

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