Search

Your search keyword '"Sulaiman Al-Ajaji"' showing total 6 results
Start Over Author "Sulaiman Al-Ajaji"
6 results on '"Sulaiman Al-Ajaji"'

1. Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly

Author

Sulaiman Al-Ajaji, Liliya Nazlamova, Taghrid Aloraini, Annie Godwin, Alexander P. Kao, Majid Alfadhel, William L. Macken, Ahmed Alfares, Htoo A. Wai, Diana Baralle, Gabrielle Wheway, Andrew G. L. Douglas, Matthew Guille, Jay E. Self, Lamia Alsubaie, Karen Stals, and Sian Ellard

Subjects
Male, Microcephaly, Coatomer, Xenopus, Intellectual disability, lcsh:Medicine, Animals, Genetically Modified, Exon, 0302 clinical medicine, CRISPR, Missense mutation, Genetics(clinical), Child, Exome, Genetics (clinical), Genetics, 0303 health sciences, biology, Syndrome, COPI, Pedigree, Xenopus model, BBSRC, Molecular Medicine, Female, lcsh:QH426-470, Adolescent, Mutation, Missense, Coatomer Protein, Cataract, 03 medical and health sciences, medicine, Animals, Humans, Family, Amino Acid Sequence, Molecular Biology, Gene, Alleles, 030304 developmental biology, BB/K019988/1, Research, lcsh:R, RCUK, Genetic Variation, COPB1, biology.organism_classification, medicine.disease, lcsh:Genetics, β-COP, 030217 neurology & neurosurgery
Abstract

Background Coat protein complex 1 (COPI) is integral in the sorting and retrograde trafficking of proteins and lipids from the Golgi apparatus to the endoplasmic reticulum (ER). In recent years, coat proteins have been implicated in human diseases known collectively as “coatopathies”. Methods Whole exome or genome sequencing of two families with a neuro-developmental syndrome, variable microcephaly and cataracts revealed biallelic variants in COPB1, which encodes the beta-subunit of COPI (β-COP). To investigate Family 1’s splice donor site variant, we undertook patient blood RNA studies and CRISPR/Cas9 modelling of this variant in a homologous region of the Xenopus tropicalis genome. To investigate Family 2’s missense variant, we studied cellular phenotypes of human retinal epithelium and embryonic kidney cell lines transfected with a COPB1 expression vector into which we had introduced Family 2’s mutation. Results We present a new recessive coatopathy typified by severe developmental delay and cataracts and variable microcephaly. A homozygous splice donor site variant in Family 1 results in two aberrant transcripts, one of which causes skipping of exon 8 in COPB1 pre-mRNA, and a 36 amino acid in-frame deletion, resulting in the loss of a motif at a small interaction interface between β-COP and β’-COP. Xenopus tropicalis animals with a homologous mutation, introduced by CRISPR/Cas9 genome editing, recapitulate features of the human syndrome including microcephaly and cataracts. In vitro modelling of the COPB1 c.1651T>G p.Phe551Val variant in Family 2 identifies defective Golgi to ER recycling of this mutant β-COP, with the mutant protein being retarded in the Golgi. Conclusions This adds to the growing body of evidence that COPI subunits are essential in brain development and human health and underlines the utility of exome and genome sequencing coupled with Xenopus tropicalis CRISPR/Cas modelling for the identification and characterisation of novel rare disease genes.

Published
2021
Full Text
View/download PDF

2. Pyogenic Liver Abscess and Papillon-Lefèvre Syndrome: Not a Rare Association

Author

Sultan Al Khenaizan, Maha Almuneef, Sulaiman Al Ajaji, and Abdullah Al-Anazi

Subjects
Male, Periodontitis, Pyogenic liver abscess, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, business.industry, Liver Abscess, Papillon–Lefèvre syndrome, Staphylococcal Infections, bacterial infections and mycoses, medicine.disease, Diagnosis, Differential, Papillon-Lefevre Disease, Palmoplantar keratoderma, Pediatrics, Perinatology and Child Health, medicine, Humans, Child, Tomography, X-Ray Computed, skin and connective tissue diseases, Complication, business
Abstract

Papillon-Lefèvre syndrome is a rare, autosomal recessive disease comprising palmoplantar keratoderma and periodontitis. Pyogenic liver abscess is an increasingly recognized complication. We report a new case of this association and review the current literature.

Published
2003
Full Text
View/download PDF

3. Phosphorylase b kinase deficiency glycogenosis with cirrhosis of the liver

Author

M.Ashraf Ali, Amir F. Kagalwalla, Y A Kagalwalla, Waldemer Gorka, and Sulaiman Al Ajaji

Subjects
Liver Cirrhosis, medicine.medical_specialty, Cirrhosis, Phosphorylase Kinase, Phosphorylase B kinase activity, Consanguinity, Hypoglycemia, Elevated serum, Culture Techniques, Internal medicine, medicine, Humans, Glycogen storage disease, Phosphorylase b, Phosphorylase B Kinase Deficiency, Phosphorylase kinase, business.industry, Glycogen Storage Disease, medicine.disease, Liver Glycogen, Endocrinology, Liver, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, business
Abstract

We describe an Arab girl with complete absence of phosphorylase b kinase activity in the liver, symptomatic hypoglycemia, and persistently elevated serum aminotransferase values whose symptoms did not lessen with age; sequential liver biopsies showed progression to cirrhosis. Cirrhosis could not be ascribed to any other known cause. We conclude that type IX glycogenosis is not always associated with a benign outcome.

Published
1995
Full Text
View/download PDF

4. Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial disease

Author

Damien Chaussabel, Guillaume Vogt, Jean-Laurent Casanova, Alexandra Y. Kreins, Satoshi Okada, Marcela Moncada-Vélez, Laurent Abel, Sulaiman Al-Ajaji, Danuta Kowalczyk, Anna Szaflarska, Ariane Chapgier, Avinash Abhyankar, Stéphanie Boisson-Dupuis, Xiao-Fei Kong, Capucine Picard, Claudia Djambas Khayat, Dieter Furthner, Saleh Al-Muhsen, Yuval Itan, Anna Macura-Biegun, Vanessa L. Bryant, Dusan Bogunovic, Steven M. Holland, Jacinta Bustamante, and Mélanie Migaud

Subjects
Heterozygote, Adolescent, Lymphocyte, Gene Expression, Mycobacterium Infections, Nontuberculous, Locus (genetics), Haploinsufficiency, Biology, Dominant-Negative Mutation, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Allele, Phosphorylation, Molecular Biology, Genetics (clinical), Exome sequencing, Cells, Cultured, Genetic Association Studies, 030304 developmental biology, Genes, Dominant, Oligonucleotide Array Sequence Analysis, Receptors, Interferon, Sequence Deletion, 0303 health sciences, B-Lymphocytes, Mycobacterium Infections, Base Sequence, Heterozygote advantage, General Medicine, Sequence Analysis, DNA, Articles, Penetrance, 3. Good health, Pedigree, medicine.anatomical_structure, Case-Control Studies, Immunology, Female, Protein Processing, Post-Translational, 030215 immunology
Abstract

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-γ). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-γ, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-γR2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN-γ-related genes. P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father. We show that the mutant allele is intrinsically loss-of-function and not dominant-negative, suggesting haploinsufficiency at the IFNGR2 locus. We also show that Epstein-Barr virus transformed B lymphocyte cells from 10 heterozygous relatives of patients with AR complete IFN-γR2 deficiency respond poorly to IFN-γ, in some cases as poorly as the cells of P1. Naive CD4(+) T cells and memory IL-4-producing T cells from these individuals also responded poorly to IFN-γ, whereas monocytes and monocyte-derived macrophages (MDMs) did not. This is consistent with the lower levels of expression of IFN-γR2 in lymphoid than in myeloid cells. Overall, MSMD in this patient is probably due to autosomal dominant (AD) IFN-γR2 deficiency, resulting from haploinsufficiency, at least in lymphoid cells. The clinical penetrance of AD IFN-γR2 deficiency is incomplete, possibly due, at least partly, to the variability of cellular responses to IFN-γ in these individuals.

Published
2012

5. Revisiting Human IL-12R beta 1 Deficiency A Survey of 141 Patients From 30 Countries

Author

Chris Nieuwhof, Yu-Lung Lau, Klara Frecerova, Suzanne T. Anderson, Vas Novelli, Dinakantha S. Kumararatne, Figen Dogu, Matías Oleastro, Barbara Pietrucha, Melike Keser, Xi-qiang Yang, Anete Sevciovic Grumach, Renate Blüetters-Sawatzki, Necil Kutukculer, Lucile Janniere, Sigifredo Pedraza, María Isabel Gaillard, Isabel Caragol, Ruth Aldana, Parisa Adimi, Orchidée Filipe-Santos, Liliane Schandené, Ludovic de Beaucoudrey, Alejandra King, Rainer Doffinger, Sergio D. Rosenzweig, Dewton Moraes-Vasconcelos, Guzide Aksu, Pamela Pui Wah Lee, Abdulaziz Al-Ghonaium, Aurélie Cobat, David Tuerlinckx, Michael Levin, Mohammed Bejaoui, Nevin Hatipoğlu, Kinda Schepers, Francisco J. Espinosa-Rosales, Andrea Bernasconi, Aydan Ikinciogullari, Jacob Levy, Mohammad S. Ehlayel, Małgorzata Pac, Darko Richter, David A. Lammas, David B. Lewis, Janine Reichenbach, Gonul Tanir, Joachim Freihorst, Tuba Turul Ozgur, Sulaiman Al-Ajaji, Masao Matsuoka, Jacqueline Feinberg, Smita Y. Patel, Abdullah A. Alangari, Judith Yancoski, Andrew Exley, Saleh Al-Muhsen, Ridha Barbouche, Tatsunori Sakai, Ana Codoceo, Xiao-Fei Kong, Claire-Anne Siegrist, Jamila El Baghdadi, Bernhard Fleckenstein, Xiaochuan Wang, Sami Al-Hajjar, Ingrid Müller-Fleckenstein, Capucine Picard, Gabriela Castro, Jean-Laurent Casanova, Tong-Xin Chen, Frans De Baets, Namik Ozbek, Alain Fischer, Liliana Bezrodnik, Aileen C. Cohen, Ariane Chapgier, Olle Jeppsson, Imen Ben-Mustapha, Saniye Gülle, Revathi Raj, Françoise Mascart, Arina Samarina, Davood Mansouri, Nima Parvaneh, Yoann Rose, Koon Wing Chan, Yuanyuan Xie, Alberto José da Silva Duarte, Ahmed Aziz Bousfiha, Claire Fieschi, Steven M. Holland, Meteran Ozen, Walther H. Haas, Stéphanie Boisson-Dupuis, Carlos Rodríguez-Gallego, Li-Ping Jiang, Ayper Somer, Suna Asilsoy, André Efira, Yaryna Boyko, Laurent Abel, Setareh Mamishi, Xiaohong Wang, Ulrich Baumann, Filomeen Haerynck, Zobaida Alsum, Kuender D Yang, Jacinta Bustamante, Daniela Di Giovani, Ozden Sanal, Maylis de Suremain, Yildiz Camcioglu, Christiane Vermylen, Ben-Zion Garty, Jutta Bernhöft, Ivelisse Natera, Suliman Al-Jumaah, Chaomin Zhu, David Nadal, Husn H. Frayha, Cigdem Aydogmus, Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, Department of Pediatrics, King Faysal Hospital and Research center, Coll Med, Prince Naif Ctr Immunol Res, King Saud University [Riyadh] (KSU), Coll Med, Dept Pediat, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Sami Ulus Children Hlth & Dis Training & Res Ctr, Ankara, Dept Pediat, King Fahad Natl Guard Hosp, Shahid Beheshti University of Medical Sciences, Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Dept Immunol, Juan Pedro Garrahan Natl Hosp Pediat, Schneider Childrens Med Ctr Israel, Hospital Universitario de Gran Canaria Dr Negrin, Immunol Lab, Vall d'Hebron University Hospital [Barcelona], Ege University, Dept Clin Biochem & Immunol, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Inflammat & Immunol Unit, Dept Pathol, Papworth Hosp NHS Fdn Trust, Inflammat & Immunol Unit, Dept Thorac Med, Karolinska University Hospital [Stockholm], Univ Childrens Hosp Zurich, Dept Infect Dis, Lviv Reg Specialized Childrens Hosp, St Marys Hosp, Imperial Coll Sch Med, Childrens Mem Hlth Inst, Immunobiol Clin, Hop Erasme, Université Libre de Bruxelles [Bruxelles] (ULB), Immunodeficiency Dept, Hop Erasme, Lab Vaccinol & Mucosal Immun, Dept Internal Med, Natl Hosp Org Kumamoto Med Ctr, Laboratory of Virus Control, Kyoto University [Kyoto], University of Geneva [Switzerland], Dept Int Relat, Minist Hlth Slovaquie, Dept Pediat Hematol & Oncol, Dept Pediat Pulmonol & Neonatol, Hannover Medical School [Hannover] (MHH), Univ Hosp Ctr Rebro, Dept Pediat Pulmonol & Immunol, Ghent University Hospital, Infect Dis Unit, Great Ormond St Hosp Sick Children, Ctr Immune Regulat, Univ Birmingham, Sch Med, MRC, Cliniques Universitaires Saint-Luc [Bruxelles], Dept Pediat, Mt Godinne Clin, Catholic University Louvain, Dept Internal Med, Div Clin & Expt Immunol, Maastricht University [Maastricht], Dept Infect Dis Epidemiol, Unit Resp Infect, Robert Koch Institute [Berlin] (RKI), Univ Erlangen Nurnberg, Pediatric Department, Ben-Gurion University of the Negev (BGU), Stanford University [Stanford], Lab Clin Infect Dis, NIAID, TMRC, NIH, Bethesda, Dept Pediat Allergy, Chang Gung Childrens Hosp, Dept Clin Immunol, Fudan University [Shanghai], Clin Immunol Lab, Chongqing Medical University, Dept Paediat & Adolescent Med, The University of Hong Kong (HKU), Universidade Federal da Bahia (UFBA), Dept Pediat,Sch Med, Shanghai Jiao Tong University [Shanghai], Univ Hosp Caracas, Hosp Ninos Luis Calvo Mackenna, Childrens Hosp Ricardo Gutierrez Buenos Aires, Dept Dermatol, Lab Invest Dermatol & Immunodeficiencies, Universidade de São Paulo (USP), Dept Pulmonol, Childrens Hosp Federico Gomez, Natl Inst Pediat, Immunodeficiencies Res Unit, Mexico City, DF, Mexico, Natl Ctr Bone Marrow Graft, Tunis, Clinical Immunology Unit, Ibn Rochd Hospital King Hassan II University-Aïn Chok, Genetics Unit, Military Hospital Mohamed V, Baskent universitesi, Dept Pediat Infect Dis & Clin Immunol, Istanbul Univ, Dept Pediat Infect Dis & Immunol, Bakirkoy Matern & Childrens State Hosp, Dr Behcet Uz Children Res & Training Hosp, Department of Pediatrics, Infectious Diseases, Cerrahpacsa Medical School, Hacettepe University = Hacettepe Üniversitesi, Fac Med Malatya, Tehran University of Medical Sciences (TUMS), Dept Biochem, Minist Hlth Mexico, Department of Pediatric and Adolescent Medicine, Hamad medical corporation, Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Çocuk Sağlığı ve Hastalıkları, Ege Üniversitesi, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rockefeller University [New York], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Shahid Beheshti University, Université libre de Bruxelles (ULB), Université Catholique de Louvain = Catholic University of Louvain (UCL), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Stanford University, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Siegrist, Claire-Anne, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), King Saud University [Riyadh] ( KSU ), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Institut Pasteur de Tunis-Réseau International des Instituts Pasteur ( RIIP ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Hannover Medical School [Hannover] ( MHH ), Robert Koch Institute [Berlin] ( RKI ), Ben-Gurion University of the Negev ( BGU ), The University of Hong Kong ( HKU ), Universidade Federal da Bahia ( UFBA ), Universidade de São Paulo ( USP ), Tehran University of Medical Sciences, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Interne Geneeskunde, RS: CARIM School for Cardiovascular Diseases, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, and UCL - (MGD) Service de pédiatrie

Subjects
Male, Proband, [SDV]Life Sciences [q-bio], Mycobacterium tuberculosis/isolation & purification, Mycobacterium bovis/isolation & purification, Disease, Interleukin-12 Receptor beta 1 Subunit - deficiency, genetics, Cytokines - blood, 0302 clinical medicine, Mycobacterium bovis - isolation & purification, Child, 0303 health sciences, ddc:618, Interleukin-12 Receptor beta 1 Subunit/*deficiency/genetics, Nontuberculous Mycobacteria/isolation & purification, biology, Age Factors, Nontuberculous Mycobacteria, Mycobacterium Infections, Nontuberculous/epidemiology/genetics, General Medicine, Middle Aged, Mycobacterium bovis, Penetrance, Mycobacteria, Atypical - isolation & purification, 3. Good health, Child, Preschool, Cytokines, Female, medicine.symptom, Adult, medicine.medical_specialty, Tuberculosis, Adolescent, Genotype, Mycobacterium Infections, Nontuberculous, Mycobacterium tuberculosis - isolation & purification, Cytokines/blood, Asymptomatic, Article, Mycobacterium tuberculosis, 03 medical and health sciences, Internal medicine, General & Internal Medicine, Interleukin-12 Receptor beta 1 Subunit, medicine, Humans, Survival analysis, 030304 developmental biology, Mycobacterium Infections, Atypical - epidemiology, genetics, [ SDV ] Life Sciences [q-bio], business.industry, Infant, Newborn, Infant, biology.organism_classification, medicine.disease, Survival Analysis, Immunology, Nontuberculous mycobacteria, business, 030215 immunology
Abstract

WOS: 000283840300002, PubMed ID: 21057261, Interleukin-12 receptor beta 1 (IL-12R beta 1) deficiency is the most common form of Mendelian susceptibility to mycobacterial disease (MSMD). We undertook an international survey of 141 patients from 102 kindreds in 30 countries. Among 102 probands, the first infection occurred at a mean age of 2.4 years. In 78 patients, this infection was caused by Bacille Calmette-Guerin (BCG; n = 65), environmental mycobacteria (EM; also known as atypical or nontuberculous mycobacteria) (n = 9) or Mycobacterium tuberculosis (n = 4). Twenty-two of the remaining 24 probands initially presented with nontyphoidal, extraintestinal salmonellosis. Twenty of the 29 genetically affected sibs displayed clinical signs (69%); however 8 remained asymptomatic (27%). Nine nongenotyped sibs with symptoms died. Recurrent BCG infection was diagnosed in 15 cases, recurrent EM in 3 cases, recurrent salmonellosis in 22 patients. Ninety of the 132 symptomatic patients had infections with a single microorganism. Multiple infections were diagnosed in 40 cases, with combined mycobacteriosis and salmonellosis in 36 individuals. BCG disease strongly protected against subsequent EM disease (p = 0.00008). Various other infectious diseases occurred, albeit each rarely, yet candidiasis was reported in 33 of the patients (23%). Ninety-nine patients (70%) survived, with a mean age at last follow-up visit of 12.7 years +/- 9.8 years (range, 0.5-46.4 yr). IL-12R beta 1 deficiency is characterized by childhood-onset mycobacteriosis and salmonellosis, rare recurrences of mycobacterial disease, and more frequent recurrence of salmonellosis. The condition has higher clinical penetrance, broader susceptibility to infections, and less favorable outcome than previously thought., Rockefeller University Center for Clinical and Translational Science [5UL1RR024143-03]; Rockefeller University; ANRFrench National Research Agency (ANR); PHRC; EUEuropean Union (EU) [LHSP-CT-2005-018736]; BNP Paribas Foundation; Dana Foundation; March of DimesMarch of Dimes; Fondation pour la Recherche MedicaleFondation pour la Recherche Medicale; Howard Hughes Medical InstituteHoward Hughes Medical Institute, The St. Giles Laboratory of Human Genetics of Infectious Diseases is supported by grants from The Rockefeller University Center for Clinical and Translational Science grant number 5UL1RR024143-03, and The Rockefeller University, ANR, PHRC, EU (LHSP-CT-2005-018736), BNP Paribas Foundation, the Dana Foundation, and the March of Dimes. LDB is supported by the Fondation pour la Recherche Medicale as part of the PhD program of Pierre et Marie Curie University (Paris, France). JLC was an International Scholar of the Howard Hughes Medical Institute.

Published
2010
Full Text
View/download PDF

6. Homozygous R396H mutation of the RAG1 gene in a Saudi infant with Omenn's syndrome: a case report

Author

Mohammed Al Balwi, Ibrahim Al Abdulkareem, Ali H. Hajeer, and Sulaiman Al Ajaji

Subjects
Medicine(all), Mutation, business.industry, T cell, hemic and immune systems, chemical and pharmacologic phenomena, General Medicine, medicine.disease, medicine.disease_cause, Recombination-activating gene, Immune system, medicine.anatomical_structure, RAG2, Case report, Immunology, Mutation testing, Medicine, Missense mutation, business, Immunodeficiency
Abstract

Introduction The V(D)J rearrangement of B and T cell lymphocytes during the recombination process, which is essential for the development of normal immune system function, depends critically on the presence of the recombination activating enzymes, RAG1 and RAG2. Mutations in RAG1 or RAG2 can lead to a spectrum of disorders, ranging from typical B-T-severe combined immunodeficiency to Omenn’s syndrome. Case presentation A two-month-old Saudi baby girl presented with fever, respiratory distress due to bronchiolitis, exfoliative erythroderma and a family history of childhood death within the first few months of life in two of her sisters who had had a similar clinical presentation to her own. Immunological work-up revealed an absence of circulating B lymphocytes, whereas various numbers of activated T lymphocytes were present in the peripheral blood and in the skin. Conclusion In this case, mutation analysis of the recombination activating genes RAG1 or RAG2 revealed a homozygous missense (c.1299G>A) mutation in the RAG1 gene. This is the first report in the literature linking a homozygous R396H mutation in the RAG1 gene with presentation of Omenn’s syndrome.

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results