scholarly journals Somatic Hypermutation Defects in Two Adult Hyper Immunoglobulin M Patients

2021 ◽  
Author(s):  
Hülya Yilmaz ◽  
Sinem Fırtına ◽  
Merve Sarıtaş ◽  
Müge Sayitoğlu ◽  
Muhlis Cem Ar
Keyword(s):  
Base Pair ◽  
Respiratory Infections ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Immunoglobulin M ◽  
Delay In Diagnosis ◽  
Targeted Next Generation Sequencing ◽  
Recessive Type ◽  
Base Pair Deletion ◽  
History Of

Abstract Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the underlying genetic variation. In this study, we identified two novel variants in AID and UNG genes, which are associated with autosomal recessive type HIGM, by targeted next generation sequencing (NGS) panel. A biallelic 11 base pair deletion (c.278_288delATGTGGCCGAC) in the coding sequence of activation-induced cytidine deaminase (AID) gene was identified in a 36-years-old patient. Biallelic two base pair insertion in exon 7 of Uracil nucleoside glycosylase (UNG) gene (c.924_925insGG) was identified in 40-years-old patient. Both variants were confirmed by Sanger sequencing. HIGM, like many of the other primary immunodeficiencies, is a rare and difficult-to-diagnose entity with heterogeneous clinical phenotypes. It should be suspected in patients with a history of early-onset recurrent respiratory infections, enlarged lymph nodes and autoimmune disorders. There might be a delay in diagnosis until adulthood especially in subtle cases or if HIGM is not included in the differential diagnosis due lacking of awareness. In this regard, genetic testing with NGS-based diagnostic panels provide a rapid and reasonable tool for the molecular diagnosis of patients with immunodeficiencies and hence, decrease the time to diagnose and prevent infection-related complications associated with increased morbidity and mortality.

Detection of in rs876657372 (delACGT) in PRSS12 Gene, Risk Factors and Associated Congenital Abnormalities in Non-Syndromic Intellectual Disability-Case Control Study.

2020 ◽  
Author(s):  
Ebtihal Mohammed Bashir Esmail ◽  
Mona Ellaithi
Keyword(s):  
Risk Factors ◽  
Intellectual Disability ◽  
Base Pair ◽  
Autosomal Recessive ◽  
Control Group ◽  
Snp Analysis ◽  
Female Ratio ◽  
Psychomotor Delay ◽  
Base Pair Deletion ◽  
History Of

Abstract BackgroundPRSS12 gene was the first gene to be identified as a cause of a non-syndromic autosomal recessive form of intellectual disability (ID). A 4-base pair deletion (delACGT; rs876657372) in the PRSS12 gene has been detected in two different families diagnosed with autosomal recessive non-syndromic intellectual disability (NS-ID). Here we aimed to find out if rs876657372 is associated with NS-ID in Sudanese and the possible risk factors that could be linked the disability.MethodsThe study included 60 individuals; 30 were diagnosed with NS-ID and 30 healthy controls. The IQ level, parent's degree of consanguinity, family history of ID, exposure to X-ray, bacterial or viral infection, smoking, and taking of medication during pregnancy were all analyzed as possible risk factors. We also investigated the possible associated congenital abnormality. Restriction fragment length polymorphism method (RFLP) was performed using primers that include the 4 base pair deletion site.ResultsMale to female ratio of 3:2 with a mean age was 15 years for both study groups. The degree of intellectual disability (ID) varies between patients group, however 60% had a moderate ID. Furthermore, 57% of the patients had consanguineous parents. Assessment of risk factors among the patient group showed mothers of the patients were more exposed to risk factors than control group. Patients’ families had history of ID more than the controls; this could indicate the possibility of autosomal recessive ID. Furthermore, Psychomotor delay appeared to be common among the patients group. The SNP analysis revealed that only two patients were heterozygous delACGT; both patients were with moderate ID. None of the control group had the mutation.ConclusionCauses of NS-ID could be correlated to certain environmental and hereditary factors. DelACGT is correlated to NS-ID mainly in patients with moderate ID.Name of the registryAl-Neelain University Institutional Review BoardTrial registration numberNU-IRB-18-5-5-22Date of registration22/05/2018

Molecular analysis of a large cohort of patients with the hyper immunoglobulin M (IgM) syndrome

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 1881-1890 ◽  
Author(s):  
Wen-I Lee ◽  
Troy R. Torgerson ◽  
Michael J. Schumacher ◽  
Leman Yel ◽  
Qili Zhu ◽  
...  
Keyword(s):  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Cd40 Ligand ◽  
Immunoglobulin M ◽  
Uracil Dna Glycosylase ◽  
Molecular Defects ◽  
Class Switch ◽  
Activation Induced Cytidine Deaminase ◽  
Cd40 Activation ◽  
Common Variable

AbstractThe hyper immunoglobulin M (IgM) syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, and defective class switch recombination and somatic hypermutation, is a heterogenous disorder with at least 5 distinct molecular defects, including mutations of the genes coding for the CD40 ligand (CD40L) and IKK-gamma (NEMO) genes, both X-linked; and mutations of CD40, activation-induced cytidine deaminase (AICDA), and uracil-DNA glycosylase (UNG), associated with autosomal recessive HIGM syndromes. To investigate the molecular basis of HIGM, we determined the prevalence of mutations affecting these 5 genes in a cohort of 140 patients (130 males and 10 females). Those patients without a molecular diagnosis were subsequently evaluated for mutations of the following genes: inducible CO-stimulator molecule (ICOS), ICOS ligand (ICOSL), and if male, Bruton tyrosine kinase (Btk) and SLAM-associated protein (SAP/SH2D1A). We found mutations of CD40L in 98 males; AICDA in 4 patients (3 males, 1 female); UNG in one adult male; and Btk in 3 boys. Of the remaining 25 males, one infant with hypohidrotic ectodermal dysplasia had a mutation of NEMO. None of the remaining 33 patients (24 males/9 females) had mutations affecting CD40, ICOS, ICOSL, or SH2D1, and are best classified as common variable immune deficiency (CVID), although other genes, including some not yet identified, may be responsible.

Detection of the Glanzmann's Thrombasthenia Mutations in Arab and Iraqi-Jewish Patients by Polymerase Chain Reaction and Restriction Analysis of Blood or Urine Samples

1991 ◽  
Vol 66 (04) ◽  
pp. 500-504 ◽  
Author(s):  
H Peretz ◽  
U Seligsohn ◽  
E Zwang ◽  
B S Coller ◽  
P J Newman
Keyword(s):  
Polymerase Chain Reaction ◽  
Base Pair ◽  
Restriction Analysis ◽  
Urine Samples ◽  
Chain Reaction ◽  
Base Pairs ◽  
Glanzmann’S Thrombasthenia ◽  
Glanzmann's Thrombasthenia ◽  
Base Pair Deletion ◽  
Polymerase Chain

SummarySevere Glanzmann's thrombasthenia is relatively frequent in Iraqi-Jews and Arabs residing in Israel. We have recently described the mutations responsible for the disease in Iraqi-Jews – an 11 base pair deletion in exon 12 of the glycoprotein IIIa gene, and in Arabs – a 13 base pair deletion at the AG acceptor splice site of exon 4 on the glycoprotein IIb gene. In this communication we show that the Iraqi-Jewish mutation can be identified directly by polymerase chain reaction and gel electrophoresis. With specially designed oligonucleotide primers encompassing the mutation site, an 80 base pair segment amplified in healthy controls was clearly distinguished from the 69 base pair segment produced in patients. Patients from 11 unrelated Iraqi-Jewish families had the same mutation. The Arab mutation was identified by first amplifying a DNA segment consisting of 312 base pairs in controls and of 299 base pairs in patients, and then digestion by a restriction enzyme Stu-1, which recognizes a site that is absent in the mutant gene. In controls the 312 bp segment was digested into 235 and 77 bp fragments, while in patients there was no change in the size of the amplified 299 bp segment. The mutation was found in patients from 3 out of 5 unrelated Arab families. Both Iraqi-Jewish and Arab mutations were detectable in DNA extracted from blood and urine samples. The described simple methods of identifying the mutations should be useful for detection of the numerous potential carriers among the affected kindreds and for prenatal diagnosis using DNA extracted from chorionic villi samples.

Mutation Spectrum in Patients with Wiskott-Aldrich Syndrome and X-linked Thrombocytopenia: Identification of Twelve Different Mutations in the WASP Gene

1996 ◽  
Vol 75 (04) ◽  
pp. 546-550 ◽  
Author(s):  
Marianne Schwartz ◽  
Albert Békássy ◽  
Mikael Donnér ◽  
Thomas Hertel ◽  
Stefan Hreidarson ◽  
...  
Keyword(s):  
Base Pair ◽  
Hot Spot ◽  
Missense Mutations ◽  
Nucleotide Substitutions ◽  
Exon 2 ◽  
Wiskott Aldrich Syndrome ◽  
Base Pair Deletion ◽  
Reliable Diagnosis ◽  
Wasp Gene ◽  
Detection Of Mutations

SummaryTwelve different mutations in the WASP gene were found in twelve unrelated families with Wiskott-Aldrich syndrome (WAS) or X-linked thrombocytopenia (XLT). Four frameshift, one splice, one nonsense mutation, and one 18-base-pair deletion were detected in seven patients with WAS. Only missense mutations were found in five patients diagnosed as having XLT. One of the nucleotide substitutions in exon 2 (codon 86) results in an Arg to Cys replacement. Two other nucleotide substitutions in this codon, R86L and R86H, have been reported previously, both giving rise to typical WAS symptoms, indicating a mutational hot spot in this codon. The finding of mutations in the WASP gene in both WAS and XLT gives further evidence of these syndromes being allelic. The relatively small size of the WASP gene facilitates the detection of mutations and a reliable diagnosis of both carriers and affected fetuses in families with WAS or XLT.

PERAN IBU DALAM PENINGKATAN SISTEM IMUN ANAK DENGAN INFEKSI SALURAN PERNAFASAN AKUT

2019 ◽  
Vol 11 (2) ◽  
pp. 79-86
Author(s):  
Cindy Ayustin Noya ◽  
Angkit Kinasih ◽  
Venti Agustina ◽  
R.Rr Maria Dyah Kurniasari
Keyword(s):  
Immune System ◽  
Acute Respiratory Infection ◽  
Lower Respiratory Tract ◽  
Research Method ◽  
Respiratory Infections ◽  
Acute Respiratory Infections ◽  
Clean Environment ◽  
History Of ◽  
Qualitative Descriptive

Infeksi saluran pernafasan akut atau yang sering disebut ISPA merupakan infeksi pada saluran pernafasan baik saluran pernafasan atas atau bawah.ISPA juga kebanyakan terjadi pada anak balita karena daya tahan tubuh mereka tidak kuat dalam menghadapi penyakit ISPA. ISPA mengakibatkan kematiansekitar15%-20% per tahun pada usia balita di Negara berkembang. Tujuan penelitian ini adalah untuk mengetahui dan menganalisa peran ibu dalam meningkatkan sistem imun anak dengan ISPA.Metode penelitian yang digunakan dalam penelitian ini adalah kualitatif deskriptif dengan sampel purposive sampling.Populasi dan sampel penelitian ini adalah ibu yang mempunyai anak dengan riwayat dan saat ini menderita penyakit ISPA di Batu Gajah Kota Ambon.Partisipan dalam penelitian ini berjumlah 5 orang. Hasil dari penelitian mendapati 4 kategori yaitu pemberian nutrisi pada anak untuk memenuhi kebutuhan agar sistem imunnya terjaga, kebersihan lingkungan, peran ibu dalam melakukan pencegahan pada anaknya yang mengalami ISPA, dan  peran ibu dalam menjaga dan mempertahankan kesehatan anaknya.   Kata kunci: peran ibu, sistem imun, ispa THE ROLE OF MOTHERS IN INCREASING IMMUNE SYSTEM OF CHILDREN WITH ACUTE RESPIRATORY INFECTION    ABSTRACT Acute respiratory infections or often called ARI is an infection of the upper or lower respiratory tract. ARI occurs mostly in children under the age of five because their endurance is not strong in dealing with ARI. ARI results in deaths of around 15%-20% per year at the age of under-five in developing countries. The purpose of this study was to determine and analyze the role of mothers in improving the immune system of children against ARI. The research method used in this study was qualitative descriptive with a purposive sampling sample. Respondents and samples of this study were five mothers who had children with a history of ARI and currently suffering from the disease in Batu Gajah, Ambon City. The results of the study found 4 categories, namely providing nutrition to children to meet their needs so that their immune systems are maintained, clean environment, mother's role in preventing children with ARI, and mother's role to preserve and maintain the health of their children. The findings indicated that in terms of coping or improving the immune system of a child to avoid ARI, it is necessary to have role the of mothers in providing nutrition so that the immune system is boosted, besides that the mother can prevent and protect her child from various diseases, especially ARI. Keywords: role of mothers, immune system, acute respiratory infections

Aspergillus Spondylodiscitis After Spinal Stenosis Surgery: A Case Report

2020 ◽  
Vol 5 (3 And 4) ◽  
pp. 155-160
Author(s):  
Mohsen Aghapoor ◽  
◽  
Babak Alijani Alijani ◽  
Mahsa Pakseresht-Mogharab ◽  
◽  
...  
Keyword(s):  
Antifungal Drugs ◽  
The Body ◽  
Lower Limbs ◽  
Lumbar Pain ◽  
Case Presentation ◽  
Delay In Diagnosis ◽  
Death Case ◽  
Therapeutic Results ◽  
History Of ◽  
Probable Diagnosis

Background and Importance: Spondylodiscitis is an inflammatory disease of the body of one or more vertebrae and intervertebral disc. The fungal etiology of this disease is rare, particularly in patients without immunodeficiency. Delay in diagnosis and treatment of this disease can lead to complications and even death. Case Presentation: A 63-year-old diabetic female patient, who had a history of spinal surgery and complaining radicular lumbar pain in both lower limbs with a probable diagnosis of spondylodiscitis, underwent partial L2 and complete L3 and L4 corpectomy and fusion. As a result of pathology from tissue biopsy specimen, Aspergillus fungi were observed. There was no evidence of immunodeficiency in the patient. The patient was treated with Itraconazole 100 mg twice a day for two months. Pain, neurological symptom, and laboratory tests improved. Conclusion: The debridement surgery coupled with antifungal drugs can lead to the best therapeutic results.

scholarly journals Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4083
Author(s):  
Asami Nishikori ◽  
Yoshito Nishimura ◽  
Rei Shibata ◽  
Koh-ichi Ohshima ◽  
Yuka Gion ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Marginal Zone Lymphoma ◽  
Immunoglobulin G4 ◽  
Intensity Index ◽  
Activation Induced Cytidine Deaminase ◽  
Systemic Disorder ◽  
Lymphoplasmacytic Infiltration ◽  
Ophthalmic Disease

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.

scholarly journals Diverse Genetic Landscape of Suspected Retinitis Pigmentosa in a Large Korean Cohort

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 675
Author(s):  
Yoon-Jeon Kim ◽  
You-Na Kim ◽  
Young-Hee Yoon ◽  
Eul-Ju Seo ◽  
Go-Hun Seo ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Detection Rate ◽  
Mutation Detection ◽  
Retinal Disease ◽  
Mutation Detection Rate ◽  
Targeted Next Generation Sequencing ◽  
Initial Symptoms ◽  
Genetic Landscape ◽  
History Of ◽  
Genetic Profiles

We conducted targeted next-generation sequencing (TGS) and/or whole exome sequencing (WES) to assess the genetic profiles of clinically suspected retinitis pigmentosa (RP) in the Korean population. A cohort of 279 unrelated Korean patients with clinically diagnosed RP and available family members underwent molecular analyses using TGS consisting of 88 RP-causing genes and/or WES with clinical variant interpretation. The combined genetic tests (TGS and/or WES) found a mutation in the 44 RP-causing genes and seven inherited retinal disease (IRD)-causing genes, and the total mutation detection rate was 57%. The mutation detection rate was higher in patients who experienced visual deterioration at a younger age (75.4%, age of symptom onset under 10 years) and who had a family history of RP (70.7%). The most common causative genes were EYS (8.2%), USH2A (6.8%), and PDE6B (4.7%), but mutations were dispersed among the 51 RP/IRD genes generally. Meanwhile, the PDE6B mutation was the most common in patients experiencing initial symptoms in their first decade, EYS in their second to third decades, and USH2A in their fifth decades and older. Of note, WES revealed some unexpected genotypes: ABCC6, CHM, CYP4V2, RS1, TGFBI, VPS13B, and WDR19, which were verified by ophthalmological re-phenotyping.

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