Leishmaniasis and Autoimmunity in Patient with LPS-Responsive Beige-Like Anchor Protein (LRBA) Deficiency

2020 ◽  
Vol 20 (3) ◽  
pp. 479-484
Author(s):  
Fereshte Salami ◽  
Afshin Shirkani ◽  
Mohammad Shahrooei ◽  
Gholamreza Azizi ◽  
Reza Yazdani ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Mutation ◽  
Immunosuppressive Drugs ◽  
Common Side Effect ◽  
Anchor Protein ◽  
Frameshift Deletion ◽  
Whole Exome ◽  
Patient Reported ◽  
Lrba Deficiency

Background/Objective: LPS-responsive beige-like anchor protein (LRBA) deficiency is a combined immunodeficiency and immune dysregulation. The authors present a case report of LPSresponsive beige-like anchor protein (LRBA) deficiency with the history of autoimmunity, enteropathy and visceral leishmaniasis. Sirolimus therapy was started for autoimmunity and enteropathy but was discontinued due to recurrent leishmaniasis. Therefore, a common side-effect of many immunosuppressive drugs in patients with LRBA deficiency is increased susceptibility to infections. Methods: Whole exome sequencing was performed to detect the underlying genetic mutation and Leishmania DNA was detected by the PCR technique in this patient. Results: Whole exome sequencing of the patient reported a homozygous frameshift deletion mutation in the LRBA gene (NM_006726: exon29: c.4638delC, p. S1546fs). Leishmania DNA PCR was positive in this case. Conclusion: Parasite infections manifestations report in LRBA deficiency. Leishmania infections in patients with chronic diarrhea and autoimmunity should be considered for immunodeficiency.

scholarly journals Infancy-Onset T1DM, Short Stature, and Severe Immunodysregulation in Two Siblings With a Homozygous LRBA Mutation

2016 ◽  
Vol 101 (3) ◽  
pp. 898-904 ◽  
Author(s):  
Felix Schreiner ◽  
Michaela Plamper ◽  
Gesche Dueker ◽  
Stefan Schoenberger ◽  
Laura Gámez-Díaz ◽  
...  
Keyword(s):  
Short Stature ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Cell Sorting ◽  
Mononuclear Cells ◽  
Fluorescence Activated Cell Sorting ◽  
Truncating Mutation ◽  
Normal Ranges ◽  
Whole Exome ◽  
Lrba Deficiency

Abstract Context: Type 1 diabetes mellitus (T1DM) is caused by autoimmunity against pancreatic β-cells. Although a significant number of T1DM patients have or will develop further autoimmune disorders during their lifetime, coexisting severe immunodysregulation is rare. Objective: Presuming autosomal-recessive inheritance in a complex immunodysregulation disorder including T1DM and short stature in two siblings, we performed whole-exome sequencing. Case Presentation: Two Libyan siblings born to consanguineous parents were presented to our diabetology department at ages 12 and 5 years, respectively. Apart from T1DM diagnosed at age 2 years, patient 1 suffered from chronic restrictive lung disease, mild enteropathy, hypogammaglobulinemia, and GH deficiency. Fluorescence-activated cell sorting analysis revealed B-cell deficiency. In addition, CD4+/CD25+ and CD25high/FoxP3+ cells were diminished, whereas an unusual CD25−/FoxP3+ population was detectable. The younger brother, patient 2, also developed T1DM during infancy. Although his enteropathy was more severe and electrolyte derangements repeatedly led to hospitalization, he did not have significant pulmonary problems. IgG levels and B-lymphocytes were within normal ranges. Results: By whole-exome sequencing we identified a homozygous truncating mutation (c.2445_2447del(C)3ins(C)2, p.P816Lfs*4) in the lipopolysaccharide-responsive beige-like anchor (LRBA) gene in both siblings. The diagnosis of LRBA deficiency was confirmed by a fluorescence-activated cell sorting-based immunoassay showing the absence of LRBA protein in phytohemagglutinin-stimulated peripheral blood mononuclear cells. Conclusion: We identified a novel truncating LRBA mutation in two siblings with T1DM, short stature, and severe immunodysregulation. LRBA mutations have previously been reported to cause multiorgan autoimmunity and immunodysfunction. In light of the variable phenotypes reported so far in LRBA-mutant individuals, LRBA deficiency should be considered in all patients presenting with T1DM and signs of severe immunodysregulation.

scholarly journals GENE-30. PRELIMINARY STUDY ON WHOLE-EXOME SEQUENCING TECHNOLOGY IN THE GENETIC ANALYSIS OF PEDIATRIC PATIENTS WITH GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi104-vi104
Author(s):  
Mingyao Lai ◽  
Juan Li ◽  
Junjie Zhen ◽  
jiangfen zhou ◽  
Qingjun Hu ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Signaling Pathways ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pediatric Patients ◽  
Genetic Mutation ◽  
Pleomorphic Xanthoastrocytoma ◽  
Pathological Examination ◽  
Sequencing Technology ◽  
Whole Exome

Abstract OBJECTIVE To analyze the genes related to the signaling pathways in pediatric gliomas and drug-related genes with whole-exome sequencing technology. METHODS The tumor tissues and matched blood samples of 17 enrolled patients were detected with whole-exome sequencing technology. There were 3 cases of diffuse midline gliomas, 2 cases of childhood glioblastomas, 3 cases of disffuse astrocytoma, 1 case of pleomorphic xanthoastrocytoma, 1 case of ganglioglioma, 6 cases of anaplastic ependymoma and 1 case of ependymoma in this study. All the enrolled patients who were no more than 14 years old received surgery in the Department of Neurosurgery, Guangdong Sanjiu Brain Hospital. The diagnosis was confirmed by pathological examination and the sample acquisition was approved by hospital ethics committee. RESULTS With the use of whole-exome sequencing technology, a total of 31 related genetic mutations were detected in 15 cases, while no genetic mutation was detected in the other 2 cases. The genes related to the signaling pathways in pediatric gliomas included ATRX, ASL1, BCOR, EP300, FGFR1, H3F3A, IGF1R, MED12, PIK3R1, PRKDC, RB1, SETD2, SMARCA4, SOX2, TGFBR2, and the drug-related genes included AKT1, BCL2, BRAF, BRCA2, CCND1, CCND2, CDK6, EGFR, FGF3, KRAS, MET, PDGFRA, PIK3CA, PTEN, TP53, TSC1. One patient only had genes related to the signaling pathways, and 14 patients had drug-related genes. CONCLUSION Applying whole-exome sequencing technology in the genetic analysis of pediatric patients with gliomas has remarkable guiding significance for revealing the mechanism of disease, searching for therapeutic targets and adopting individualized treatment, which can bring potential benefits to pediatric patients. However, more samples and further data analysis and verification are needed in future study.

scholarly journals Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 900 ◽  
Author(s):  
Shamsudheen Karuthedath Vellarikkal ◽  
Rijith Jayarajan ◽  
Ankit Verma ◽  
Sreelata Nair ◽  
Rowmika Ravi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epidermolysis Bullosa ◽  
Sporadic Case ◽  
The Body ◽  
Epidermolysis Bullosa Simplex ◽  
Dominant Form ◽  
Dystrophic Epidermolysis Bullosa ◽  
Frameshift Deletion ◽  
Whole Exome

Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB) is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

Genetic mutation as biomarker for advanced cancer patients receiving apatinib: An analysis based on whole exome sequencing.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e24219-e24219
Author(s):  
Yong Fang ◽  
Yulong Zheng ◽  
Jun Chen ◽  
Jieer Ying ◽  
Haizhou Lou ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Cancer Patients ◽  
Whole Exome Sequencing ◽  
Advanced Cancer ◽  
Genetic Mutation ◽  
Advanced Cancer Patients ◽  
Whole Exome

scholarly journals Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 900 ◽  
Author(s):  
Shamsudheen Karuthedath Vellarikkal ◽  
Rijith Jayarajan ◽  
Ankit Verma ◽  
Sreelata Nair ◽  
Rowmika Ravi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Epidermolysis Bullosa ◽  
Sporadic Case ◽  
The Body ◽  
Epidermolysis Bullosa Simplex ◽  
Dominant Form ◽  
Dystrophic Epidermolysis Bullosa ◽  
Frameshift Deletion ◽  
Whole Exome

Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse inherited skin fragility disorder. It is majorly manifested by appearance of epidermal bullae upon friction caused either by physical or environmental trauma. The phenotypic manifestations also include appearance of milia, scarring all over the body and nail dystrophy. DEB can be inherited in a recessive or dominant form and the recessive form of DEB (RDEB) is more severe. In the present study, we identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift Collagen VII mutation to the repertoire of known mutations reported in the disease, to the best of our knowledge, this is the first report of a genetically characterized case of DEB from India.

Whole Exome Sequencing (WES) in Familien mit linksventrikulärer Ausfluβtraktobstruktion (LVOTO)

2014 ◽  
Vol 62 (S 02) ◽  
Author(s):  
M. Hitz ◽  
S. Al-Turki ◽  
A. Schalinski ◽  
U. Bauer ◽  
T. Pickardt ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome
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