Clinical characteristics and genetic analysis of 3 A20 Haploinsufficiency patients

2021 ◽  
Author(s):  
Dan Zhang ◽  
Zhixuan Zhou ◽  
Jianming Lai ◽  
Gaixiu Su
Keyword(s):  
Genetic Testing ◽  
Age Of Onset ◽  
Immunosuppressive Agents ◽  
Disease Patient ◽  
Gastrointestinal Symptoms ◽  
Coombs Test ◽  
Gradual Improvement ◽  
Genetic Characteristics ◽  
Tnfaip3 Gene ◽  
Oral Ulcers

Abstract Backguound To evaluate the clinical and genetic characteristics of 3 children with HA20. Methods The clinical and genetic testing data of 3 children with HA20 treated at CIP between August 2016 and October 2019 were retrospectively analysed. Results Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. For laboratory examination, In patient 1, the WBC,CRP and AESR showed high. In patient 2, the WBC was normal, but CRP and AESR showed high. In patient 3, the WBC, CRP, and AESR showed high. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that the 3 patients were heterozygous for mutations in the TNFAIP3 gene. For treatment, patient 1 used TNFα antagonist and thalidomide, patient 2 used TNFαantagonist and sulfasalazine, and patient 3 used hormones and thalidomide. Patients 1 and 2 were followed up for 4 and 3 months, respectively. There was improvement in joint and gastrointestinal symptoms, inflammatory indices and RF were normal, dsDNA and Coombs test became negative. Patient 3 was treated at an outside hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in the TNFAIP3 gene. It presents clinically as a Behçet-like syndrome and can present as various other autoimmune diseases as well. Hormones and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with an early age of onset or Behçet-like presentation to achieve early diagnosis and accurate treatment.

scholarly journals Analysis of the Clinical and Genetic Characteristics of 3 Cases of A20 Haploinsufficiency

2020 ◽  
Author(s):  
Dan Zhang ◽  
Zhixuan Zhou ◽  
Jianming Lai ◽  
Gaixiu Su
Keyword(s):  
Genetic Testing ◽  
Age Of Onset ◽  
Immunosuppressive Agents ◽  
Disease Patient ◽  
Gastrointestinal Symptoms ◽  
Coombs Test ◽  
Gradual Improvement ◽  
Genetic Characteristics ◽  
Tnfaip3 Gene ◽  
Oral Ulcers

Abstract Background To evaluate the clinical and genetic characteristics of 3 children with HA20. Methods The clinical and genetic testing data of 3 children with HA20 treated at CIP between August 2016 and October 2019 were retrospectively analysed. Results Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. For laboratory examination, In patient 1, the WBC,CRP and AESR showed high. In patient 2, the WBC was normal, but CRP and AESR showed high. In patient 3, the WBC, CRP, and AESR showed high. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that the 3 patients were heterozygous for mutations in the TNFAIP3 gene. For treatment, patient 1 used TNFα antagonist and thalidomide, patient 2 used TNFαantagonist and sulfasalazine, and patient 3 used hormones and thalidomide. Patients 1 and 2 were followed up for 4 and 3 months, respectively. There was improvement in joint and gastrointestinal symptoms, inflammatory indices and RF were normal, dsDNA and Coombs test became negative. Patient 3 was treated at an outside hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in the TNFAIP3 gene. It presents clinically as a Behçet-like syndrome and can present as various other autoimmune diseases as well. Hormones and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with an early age of onset or Behçet-like presentation to achieve early diagnosis and accurate treatment.

scholarly journals Clinical characteristics and genetic analysis of A20 haploinsufficiency

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Zhang ◽  
Gaixiu Su ◽  
Zhixuan Zhou ◽  
Jianming Lai
Keyword(s):  
Genetic Testing ◽  
Rheumatoid Factor ◽  
Immunosuppressive Agents ◽  
Disease Patient ◽  
Coombs Test ◽  
Gradual Improvement ◽  
Genetic Characteristics ◽  
Tnfaip3 Gene ◽  
Oral Ulcers ◽  
Tnf Α

Abstract Purpose To evaluate the clinical and genetic characteristics of 3 children with Haploinsufficiency of A20 (HA20). Methods:The clinical and genetic testing data of 3 children with HA20 treated at Capital Institute of Pediatrics (CIP) between August 2016 and October 2019 were retrospectively analysed. Result Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. Regarding laboratory tests, patients were found to have elevated white blood cell (WBC) count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The CRP and ESR was reported to be high in all the patients. The WBC was reported to be high in patient 1 and 3. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene. As for the treatment, patient 1 was treated with TNFα antagonist, patient 2 was treated with TNF α antagonist and sulfasalazine, and patient 3 was treated with corticosteroids and thalidomide. Patients 1 and 2 were followed for four and 3 months, respectively. There was an improvement in joint and gastrointestinal symptoms; inflammatory indices and rheumatoid factor (RF) were normal, and dsDNA and Coombs test became negative. Patient 3 was treated at another hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene. It may present as Behçet-like syndrome and resemble various other autoimmune diseases as well. Corticosteroids and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with early-age onset or Behçet-like syndrome to achieve early diagnosis and accurate treatment.

scholarly journals Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Zhang ◽  
Gaixiu Su ◽  
Yan Liu ◽  
Jianming Lai
Keyword(s):  
Genetic Testing ◽  
Pyoderma Gangrenosum ◽  
White Blood Cells ◽  
Skin Lesions ◽  
Coombs Test ◽  
Genetic Characteristics ◽  
Normal Patient ◽  
Angina Patient ◽  
Reactive Protein ◽  
Pyogenic Arthritis

Abstract Objective To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Methods This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020. Results One male and two female children were 6 years and 5 months, 8 years and 7 months, and 13 years and 3 months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig’s angina. Patient 2 had pyogenic arthritis, and pyoderma gangrenosum. Patient 3 had hepatomegaly, pyogenic arthritis, and pulmonary hypertension. Laboratory tests revealed that all three children had elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patient 1: C-antineutrophilic cytoplasmic antibodies(c-ANCA), positive; antiglobulin test (Coombs), positive. Patient 2: blood zinc, 4.38 mg/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, β2 glycoprotein I, positive; Coombs test, positive; RF, 28.3 U/ml (elevated); C3, 0.77 g/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G > A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8 months. The patient did not develop new skin lesions. The blood count showed mild neutropenia. The spleen was considerably retracted and the CRP became normal. Patient 2 was treated with etanercept and methylprednisolone. The patient had no further arthralgias and pyoderma gangrenosum showed improvement. The spleen was smaller than before. White blood cells were shown to be approximately 2–3 × 109/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient’s joint symptoms disappeared gradually and the liver retracted markedly. The pulmonary artery pressure returned to normal. Moreover, Coombs test result was negative. CRP and AESR were lower than before. Conclusion PAMI syndrome can manifest as pyogenic arthritis, pyoderma gangrenosum, acne, and trilineage hypoplasia, as well as autoimmune diseases. Glucocorticoid and immunosuppressive therapy are partially effective and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing is helpful to confirm diagnosis.

scholarly journals Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 997
Author(s):  
Sophie E. van Peer ◽  
Corine J. H. Pleijte ◽  
Ronald R. de Krijger ◽  
Marjolijn C. J. Jongmans ◽  
Roland P. Kuiper ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Testing ◽  
Renal Tumor ◽  
Molecular Characteristics ◽  
Extensive Literature ◽  
Cystic Nephroma ◽  
Limited Information ◽  
Review Of The Literature ◽  
Genetic Characteristics ◽  
Excellent Outcome

In children presenting with a predominantly cystic renal tumor, the most likely diagnoses include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both entities are rare and limited information on the clinical and molecular characteristics, treatment, and outcome is available since large cohort studies are lacking. We performed an extensive literature review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN and CN was 12 months (range: 3 weeks–4 years) and 16 months (prenatal diagnosis–16 years), respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities. Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none directly due to disease. In conclusion, children with CPDN and CN are young, do not present with metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and genetic testing is important. International registration of cystic renal tumor cohorts is required to enable a better understanding of clinical and genetic characteristics.

Frequency and characterization of mutations in genes in a large cohort of patients referred to MODY registry

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emily Breidbart ◽  
Liyong Deng ◽  
Patricia Lanzano ◽  
Xiao Fan ◽  
Jiancheng Guo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Exome Sequencing ◽  
Large Scale ◽  
Age Of Onset ◽  
Family Members ◽  
Ethnically Diverse ◽  
Monogenic Diabetes ◽  
Diabetes Diagnosis ◽  
Pathogenic Variants ◽  
Atypical Diabetes

Abstract Objectives There have been few large-scale studies utilizing exome sequencing for genetically undiagnosed maturity onset diabetes of the young (MODY), a monogenic form of diabetes that is under-recognized. We describe a cohort of 160 individuals with suspected monogenic diabetes who were genetically assessed for mutations in genes known to cause MODY. Methods We used a tiered testing approach focusing initially on GCK and HNF1A and then expanding to exome sequencing for those individuals without identified mutations in GCK or HNF1A. The average age of onset of hyperglycemia or diabetes diagnosis was 19 years (median 14 years) with an average HbA1C of 7.1%. Results Sixty (37.5%) probands had heterozygous likely pathogenic/pathogenic variants in one of the MODY genes, 90% of which were in GCK or HNF1A. Less frequently, mutations were identified in PDX1, HNF4A, HNF1B, and KCNJ11. For those probands with available family members, 100% of the variants segregated with diabetes in the family. Cascade genetic testing in families identified 75 additional family members with a familial MODY mutation. Conclusions Our study is one of the largest and most ethnically diverse studies using exome sequencing to assess MODY genes. Tiered testing is an effective strategy to genetically diagnose atypical diabetes, and familial cascade genetic testing identified on average one additional family member with monogenic diabetes for each mutation identified in a proband.

scholarly journals Preimplantation genetic testing for aneuploidy in uterus transplant patients

2021 ◽  
Vol 15 ◽  
pp. 263349412110098
Author(s):  
Rhea Chattopadhyay ◽  
Elliott Richards ◽  
Valerie Libby ◽  
Rebecca Flyckt
Keyword(s):  
Genetic Testing ◽  
In Vitro Fertilization ◽  
Immunosuppressive Agents ◽  
Live Birth Rate ◽  
Preimplantation Genetic Testing ◽  
Vitro Fertilization ◽  
Uterus Transplantation ◽  
Advantages And Disadvantages ◽  
Dilation And Curettage

Uterus transplantation is an emerging treatment for uterine factor infertility. In vitro fertilization with cryopreservation of embryos prior is required before a patient can be listed for transplant. Whether or not to perform universal preimplantation genetic testing for aneuploidy should be addressed by centers considering a uterus transplant program. The advantages and disadvantages of preimplantation genetic testing for aneuploidy in this unique population are presented. The available literature is reviewed to determine the utility of preimplantation genetic testing for aneuploidy in uterus transplantation protocols. Theoretical benefits of preimplantation genetic testing for aneuploidy include decreased time to pregnancy in a population that benefits from minimization of exposure to immunosuppressive agents and decreased chance of spontaneous abortion requiring a dilation and curettage. Drawbacks include increased cost per in vitro fertilization cycle, increased number of required in vitro fertilization cycles to achieve a suitable number of embryos prior to listing for transplant, and a questionable benefit to live birth rate in younger patients. Thoughtful consideration of whether or not to use preimplantation genetic testing for aneuploidy is necessary in uterus transplant trials. Age is likely a primary factor that can be useful in determining which uterus transplant recipients benefit from preimplantation genetic testing for aneuploidy.

A case of Graves’ disease associated with membranoproliferative glomerulonephritis and leukocytoclastic vasculitis

2018 ◽  
Vol 31 (10) ◽  
pp. 1165-1168 ◽  
Author(s):  
Werner Keenswijk ◽  
Eva Degraeuwe ◽  
Anne Hoorens ◽  
Jo Van Dorpe ◽  
Johan Vande Walle
Keyword(s):  
Renal Function ◽  
Membranoproliferative Glomerulonephritis ◽  
Leukocytoclastic Vasculitis ◽  
White Cell Count ◽  
Gastrointestinal Symptoms ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Complement Factor ◽  
Gradual Improvement ◽  
Complement Factor C3

Abstract Background The association of hyperthyroidism with renal disease is very rare and the importance of timely clinical recognition cannot be overemphasized. Case presentation An 11-year-old girl presented with gastrointestinal symptoms while hypertension, edema and abdominal pain were noticed on clinical examination. Laboratory investigation revealed: hemoglobin 9.4 (11.5–15.5) g/dL, total white cell count 16 (4.5–12)×109/L, platelets 247 (150–450)×109/L, C-reactive protein (CRP) 31.8 (<5) mg/L, blood urea nitrogen (BUN) 126 (13–43) mg/dL, creatinine 0.98 (0.53–0.79) mg/dL, albumin 25 (35–52) g/dL, complement factor C3 0.7 (0.9–1.8) g/L, complement factor C4 0.1 (0.1–0.4) g/L, tri-iodothyronine 6.5 (2.5–5.2) pg/mL, free thyroxine 2.4 (1–1.7) ng/dL, thyroid stimulating hormone (TSH) <0.02 (0.5–4.3) mU/L. Urinalysis showed nephrotic range proteinuria. Renal function deteriorated necessitating hemodialysis (HD). A renal biopsy revealed an immune complex-mediated membranoproliferative glomerulonephritis (MPGN). Elevated thyroid hormones and suppressed TSH levels with elevated thyroperoxidase antibodies and thyroid stimulating immunoglobulins confirmed the diagnosis of Graves’ disease. Corticosteroids were commenced and eventually thiamazole was added with gradual improvement of renal function, cessation of HD and discharge from the hospital. Conclusions Graves’ disease complicated by MPGN is extremely rare, but can cause life-threatening complications.

A possible case of serum sickness after ocrelizumab infusion

2020 ◽  
Vol 27 (1) ◽  
pp. 155-158 ◽  
Author(s):  
Vanessa F Moreira Ferreira ◽  
Dorlan J Kimbrough ◽  
James M Stankiewicz
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibodies ◽  
Maintenance Dose ◽  
Gastrointestinal Symptoms ◽  
Serum Sickness ◽  
Intermittent Fever ◽  
Gradual Improvement ◽  
Significant Complication

A 41-year-old female diagnosed with multiple sclerosis began ocrelizumab treatment. She received her first treatment course without significant complication. After receiving the first maintenance dose 6 months later, she developed weakness, myalgias, gastrointestinal symptoms, headache, and intermittent fever persisting for 4 weeks. A working diagnosis of serum sickness was determined after excluding other probable entities. She received 3 days of 1 g methylprednisolone intravenously and five plasma exchanges, experiencing gradual improvement. Serum sickness has occurred with monoclonal antibodies including rituximab. This case of possible ocrelizumab-associated serum sickness suggests that clinicians should remain vigilant about this possibility with this medication.

scholarly journals A case of intestinal Behcet’s disease under Adalimumab

2017 ◽  
Vol 4 (3) ◽  
pp. 62
Author(s):  
David T. Dulaney ◽  
Wassem Juakiem ◽  
Katherine Cebe ◽  
Angelo H. Paredes
Keyword(s):  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Immunosuppressive Agents ◽  
African American Female ◽  
Behcet's Disease ◽  
Oral Ulcers ◽  
Adalimumab Therapy ◽  
Tnfα Inhibitors ◽  
Tnfα Inhibitor

Behcet’s disease (BD) is a multisystem mucocutaneous inflammatory condition characterized by recurrent genital and oral ulcers, ocular inflammation, and can involve the gastrointestinal tract. Treatment involves the usage of immunosuppressive agents to control the disease with glucocorticoids utilized for treatment of flares. Tumor necrosis factor inhibitors are frequently used to control the disease as well. We present the case of a 40 years old African American female presenting with intestinal BD that was refractory to adalimumab therapy. In conjunction with glucocorticoids, the patient’s intestinal disease was controlled with infliximab therapy. Currently, there have been no studies comparing the efficacy of TNFα inhibitors on the treatment of BD. Future studies are needed to compare the efficacy of TNFα inhibitor agents in the treatment of intestinal manifestations of BD.

Defining early-onset kidney cancer: Implications for genetic counseling.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 342-342 ◽  
Author(s):  
Brian Shuch ◽  
Srinivas Vourganti ◽  
Lindsay Middleton ◽  
W. Marston Linehan
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Kidney Cancer ◽  
Age Of Onset ◽  
Age Distribution ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Specific Syndrome ◽  
Number Of Patients ◽  
Genetic Testing Guidelines

342 Background: Approximately 1-4% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC genetic counseling. We evaluate how age of onset could guide referral for genetic testing. Methods: We analyzed the age distribution of RCC cases in the Surveillance and Epidemiology and End Results (SEER-17) program and from our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary syndrome. Models were established to evaluate the specific age thresholds for genetic counseling. Results: The median age of RCC in SEER-17 was 64 years old with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (p < 0.05). The bottom decile overall was 46 years of age and slightly differed by sex, race, and histology. The mean and median age of 608 cases of hereditary kidney cancer was 39.3 and 37 years old. While age varied by specific syndrome, 70% of the hereditary cases lied below the bottom age decile. Modeling demonstrated that age alone could limit the number of patients for counseling and that the 10th percentile maximized sensitivity and specificity. Conclusions: Besides associated clinical manifestations and personal/family history, early age of onset in RCC could be a sign of a hereditary kidney cancer. In the absence of clinical signs, an age of onset ≤46 should trigger referral for genetic counseling and may serve as a useful cutoff when establishing genetic testing guidelines.

Sign in / Sign up

Export Citation Format

Share Document