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Immunodeficiency 62(IMD62)

MedGen UID:: 1673905
•Concept ID:: C5193109
•: Disease or Syndrome

Synonyms:	IMD62; IMMUNODEFICIENCY 62

Gene (location): Gene(s) directly associated with this condition or phenotype.	ARHGEF1 (19q13.2)

Monarch Initiative:	MONDO:0032763
OMIM®:	618459

Definition

Immunodeficiency-62 (IMD62) is an autosomal recessive primary immunologic disorder clinically characterized by onset of recurrent upper and lower respiratory infections late in the first decade of life. Patients may also have increased viral susceptibility to varicella zoster virus (VZV) or herpes simplex virus (HSV). Laboratory studies show impaired antibody response to vaccination, low levels of circulating memory B cells, and almost undetectable antibodies. There is also evidence of secondary T-cell dysfunction. The disorder may result from disturbed actin cytoskeleton dynamics causing impaired lymphocyte migration (summary by Bouafia et al., 2019). [from OMIM]

Clinical features

From HPO

Bronchiectasis

MedGen UID:: 14234
•Concept ID:: C0006267
•: Disease or Syndrome

Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.

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Recurrent upper respiratory tract infections

MedGen UID:: 154380
•Concept ID:: C0581381
•: Disease or Syndrome

An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).

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Recurrent lower respiratory tract infections

MedGen UID:: 756211
•Concept ID:: C3163798
•: Disease or Syndrome

An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.

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Decreased circulating total IgM

MedGen UID:: 116095
•Concept ID:: C0239989
•: Finding

An abnormally decreased level of immunoglobulin M (IgM) in blood.

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Autoimmune thrombocytopenia

MedGen UID:: 116621
•Concept ID:: C0242584
•: Disease or Syndrome

The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.

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Varicella, severe recurrent

MedGen UID:: 322202
•Concept ID:: C1833487
•: Disease or Syndrome

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B lymphocytopenia

MedGen UID:: 340780
•Concept ID:: C1855067
•: Finding

An abnormal decrease from the normal count of B cells.

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Recurrent herpes

MedGen UID:: 870750
•Concept ID:: C4025207
•: Finding

Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus.

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Decreased proportion of memory B cells

MedGen UID:: 893145
•Concept ID:: C4072913
•: Finding

A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).

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Increased proportion of transitional B cells

MedGen UID:: 892766
•Concept ID:: C4072920
•: Finding

An elevation in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.

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Reduced isohemagglutinin level

MedGen UID:: 1700218
•Concept ID:: C5139157
•: Finding

Level of isohemagglutinin reduced below expected concentration. An isohemagglutinin refers to the naturally occurring antibodies in the ABO blood group system (i.e., anti-A in a group B person, anti-B in a group A person, and anti-A, anti-B, and anti-A,B in a group O person).

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Complete or near-complete absence of specific antibody response to tetanus vaccine

MedGen UID:: 1687415
•Concept ID:: C5139458
•: Finding

The inability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination.

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Decreased circulating IgG concentration

MedGen UID:: 1720114
•Concept ID:: C5234937
•: Finding

An abnormally decreased level of immunoglobulin G (IgG) in blood.

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Abnormality of the immune system
Abnormality of the respiratory system

Professional guidelines

PubMed

Survival in primary hemophagocytic lymphohistiocytosis, 2016 to 2021: etoposide is better than its reputation.

Böhm S, Wustrau K, Pachlopnik Schmid J, Prader S, Ahlmann M, Yacobovich J, Beier R, Speckmann C, Behnisch W, Ifversen M, Jordan M, Marsh R, Naumann-Bartsch N, Mauz-Körholz C, Hönig M, Schulz A, Malinowska I, Hines M, Nichols KE, Gil-Herrera J, Talano JA, Crooks B, Formankova R, Jorch N, Bakhtiar S, Kühnle I, Streiter M, Nathrath M, Russo A, Dürken M, Lang P, Lindemans C, Henter JI, Lehmberg K, Ehl S
Blood 2024 Mar 7;143(10):872-881. doi: 10.1182/blood.2023022281. PMID: 37992218

A Comprehensive Management Approach in Pediatric and Adolescent Patients With Hereditary Angioedema.

Tachdjian R, Kaplan AP
Clin Pediatr (Phila) 2023 Oct;62(9):973-980. Epub 2023 Mar 12 doi: 10.1177/00099228231155703. PMID: 36908071 Free PMC Article

Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects.

Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, Wolff D, Hoshino A, Kobayashi M, Imai K, Takagi M, Dybedal I, Haddock JA, Sansom DM, Lucena JM, Seidl M, Schmitt-Graeff A, Reiser V, Emmerich F, Frede N, Bulashevska A, Salzer U, Schubert D, Hayakawa S, Okada S, Kanariou M, Kucuk ZY, Chapdelaine H, Petruzelkova L, Sumnik Z, Sediva A, Slatter M, Arkwright PD, Cant A, Lorenz HM, Giese T, Lougaris V, Plebani A, Price C, Sullivan KE, Moutschen M, Litzman J, Freiberger T, van de Veerdonk FL, Recher M, Albert MH, Hauck F, Seneviratne S, Pachlopnik Schmid J, Kolios A, Unglik G, Klemann C, Speckmann C, Ehl S, Leichtner A, Blumberg R, Franke A, Snapper S, Zeissig S, Cunningham-Rundles C, Giulino-Roth L, Elemento O, Dückers G, Niehues T, Fronkova E, Kanderová V, Platt CD, Chou J, Chatila TA, Geha R, McDermott E, Bunn S, Kurzai M, Schulz A, Alsina L, Casals F, Deyà-Martinez A, Hambleton S, Kanegane H, Taskén K, Neth O, Grimbacher B
J Allergy Clin Immunol 2018 Dec;142(6):1932-1946. Epub 2018 May 4 doi: 10.1016/j.jaci.2018.02.055. PMID: 29729943 Free PMC Article

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Recent clinical studies

Etiology

Heterogeneity in RAG1 and RAG2 deficiency: 35 cases from a single-centre.

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Clin Exp Immunol 2024 Feb 7;215(2):160-176. doi: 10.1093/cei/uxad110. PMID: 37724703 Free PMC Article

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Leiding JW, Vogel TP, Santarlas VGJ, Mhaskar R, Smith MR, Carisey A, Vargas-Hernández A, Silva-Carmona M, Heeg M, Rensing-Ehl A, Neven B, Hadjadj J, Hambleton S, Ronan Leahy T, Meesilpavikai K, Cunningham-Rundles C, Dutmer CM, Sharapova SO, Taskinen M, Chua I, Hague R, Klemann C, Kostyuchenko L, Morio T, Thatayatikom A, Ozen A, Scherbina A, Bauer CS, Flanagan SE, Gambineri E, Giovannini-Chami L, Heimall J, Sullivan KE, Allenspach E, Romberg N, Deane SG, Prince BT, Rose MJ, Bohnsack J, Mousallem T, Jesudas R, Santos Vilela MMD, O'Sullivan M, Pachlopnik Schmid J, Průhová Š, Klocperk A, Rees M, Su H, Bahna S, Baris S, Bartnikas LM, Chang Berger A, Briggs TA, Brothers S, Bundy V, Chan AY, Chandrakasan S, Christiansen M, Cole T, Cook MC, Desai MM, Fischer U, Fulcher DA, Gallo S, Gauthier A, Gennery AR, Gonçalo Marques J, Gottrand F, Grimbacher B, Grunebaum E, Haapaniemi E, Hämäläinen S, Heiskanen K, Heiskanen-Kosma T, Hoffman HM, Gonzalez-Granado LI, Guerrerio AL, Kainulainen L, Kumar A, Lawrence MG, Levin C, Martelius T, Neth O, Olbrich P, Palma A, Patel NC, Pozos T, Preece K, Lugo Reyes SO, Russell MA, Schejter Y, Seroogy C, Sinclair J, Skevofilax E, Suan D, Suez D, Szabolcs P, Velasco H, Warnatz K, Walkovich K, Worth A; STAT3 GOF Working Group members, Seppänen MRJ, Torgerson TR, Sogkas G, Ehl S, Tangye SG, Cooper MA, Milner JD, Forbes Satter LR
J Allergy Clin Immunol 2023 Apr;151(4):1081-1095. Epub 2022 Oct 11 doi: 10.1016/j.jaci.2022.09.002. PMID: 36228738 Free PMC Article

Waldenström macroglobulinemia and relationship to immune deficiency.

Levy A, Guidez S, Debiais C, Princet I, Bouyer S, Dindinaud E, Delwail V, Systchenko T, Moya N, Gruchet C, Sabirou F, Bobin A, Gardeney H, Nsiala L, Cailly L, Olivier G, Motard C, Fleck E, Corby A, Roul C, Denis G, Dieval C, Leleu X, Tomowiak C
Leuk Lymphoma 2021 Nov;62(11):2665-2670. Epub 2021 Jun 4 doi: 10.1080/10428194.2021.1907379. PMID: 34085595

Inflammation, a significant player of Ataxia-Telangiectasia pathogenesis?

Zaki-Dizaji M, Akrami SM, Azizi G, Abolhassani H, Aghamohammadi A
Inflamm Res 2018 Jul;67(7):559-570. Epub 2018 Mar 26 doi: 10.1007/s00011-018-1142-y. PMID: 29582093

Transfusion-associated graft-versus-host disease.

Rühl H, Bein G, Sachs UJ
Transfus Med Rev 2009 Jan;23(1):62-71. doi: 10.1016/j.tmrv.2008.09.006. PMID: 19056035

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Diagnosis

Mpox in people with advanced HIV infection: a global case series.

Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS, Corral Herrera EA, Crabtree-Ramirez B, Blanco JL, Girometti N, Mazzotta V, Hazra A, Silva M, Montenegro-Idrogo JJ, Gebo K, Ghosn J, Peña Vázquez MF, Matos Prado E, Unigwe U, Villar-García J, Wald-Dickler N, Zucker J, Paredes R, Calmy A, Waters L, Galvan-Casas C, Walmsley S, Orkin CM; SHARE-NET writing group
Lancet 2023 Mar 18;401(10380):939-949. Epub 2023 Feb 21 doi: 10.1016/S0140-6736(23)00273-8. PMID: 36828001

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Early Diagnosis of Primary Immunodeficiency Disease Using Clinical Data and Machine Learning.

Mayampurath A, Ajith A, Anderson-Smits C, Chang SC, Brouwer E, Johnson J, Baltasi M, Volchenboum S, Devercelli G, Ciaccio CE
J Allergy Clin Immunol Pract 2022 Nov;10(11):3002-3007.e5. Epub 2022 Sep 13 doi: 10.1016/j.jaip.2022.08.041. PMID: 36108921

Waldenström macroglobulinemia and relationship to immune deficiency.

Transfusion-associated graft-versus-host disease.

Rühl H, Bein G, Sachs UJ
Transfus Med Rev 2009 Jan;23(1):62-71. doi: 10.1016/j.tmrv.2008.09.006. PMID: 19056035

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Therapy

Interventions for improving health literacy in migrants.

Baumeister A, Aldin A, Chakraverty D, Hübner C, Adams A, Monsef I, Skoetz N, Kalbe E, Woopen C
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Digital, Crowdsourced, Multilevel Intervention to Promote HIV Testing Among Men Who Have Sex With Men: Cluster Randomized Controlled Trial.

Lin Y, Ren C, Liao M, Kang D, Li C, Jiao K, Wang L, Yan Y, Li Y, Wu T, Cheng C, Zhao Z, Xu Z, Tang W, Tucker JD, Ma W
J Med Internet Res 2023 Oct 30;25:e46890. doi: 10.2196/46890. PMID: 37902831 Free PMC Article

Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients.

Labrosse R, Barmettler S, Derfalvi B, Blincoe A, Cros G, Lacombe-Barrios J, Barsalou J, Yang N, Alrumayyan N, Sinclair J, Ong MS, Camargo CA Jr, Walter J, Haddad E
J Allergy Clin Immunol 2021 Aug;148(2):523-532.e8. Epub 2021 Apr 20 doi: 10.1016/j.jaci.2021.03.041. PMID: 33862010

A review of factors influencing the incidence and severity of plaque-induced gingivitis.

Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

Darunavir: in the treatment of HIV-1 infection.

Fenton C, Perry CM
Drugs 2007;67(18):2791-801. doi: 10.2165/00003495-200767180-00010. PMID: 18062724

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Prognosis

Wiskott-Aldrich syndrome: a study of 577 patients defines the genotype as a biomarker for disease severity and survival.

Vallée TC, Glasmacher JS, Buchner H, Arkwright PD, Behrends U, Bondarenko A, Browning MJ, Buchbinder D, Cattoni A, Chernyshova L, Ciznar P, Cole T, Czogała W, Dueckers G, Edgar JDM, Erbey F, Fasth A, Ferrua F, Formankova R, Gambineri E, Gennery AR, Goldman FD, Gonzalez-Granado LI, Heilmann C, Heiskanen-Kosma T, Juntti H, Kainulainen L, Kanegane H, Karaca NE, Kilic SS, Klein C, Kołtan S, Kondratenko I, Meyts I, Nasrullayeva GM, Notarangelo LD, Pasic S, Pellier I, Pignata C, Misbah S, Schulz A, Segundo GR, Shcherbina A, Slatter M, Sokolic R, Soler-Palacin P, Stepensky P, van Montfrans JM, Ryhänen S, Wolska-Kuśnierz B, Ziegler JB, Zhao X, Aiuti A, Ochs HD, Albert MH
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Waldenström macroglobulinemia and relationship to immune deficiency.

Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV: Systematic Review and Meta-Analysis.

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Circulation 2018 Sep 11;138(11):1100-1112. doi: 10.1161/CIRCULATIONAHA.117.033369. PMID: 29967196 Free PMC Article

Human T-lymphotropic virus type 1 infection and disease in Spain.

de Mendoza C, Caballero E, Aguilera A, Requena S, de Lejarazu RO, Pirón M, González R, Jiménez A, Roc L, Treviño A, Benito R, Fernández-Alonso M, Aguinaga A, Rodríguez C, García-Costa J, Blanco L, Ramos JM, Calderón E, Eirós JM, Sauleda S, Barreiro P, Soriano V; Spanish HTLV Network
AIDS 2017 Jul 31;31(12):1653-1663. doi: 10.1097/QAD.0000000000001527. PMID: 28700391

A review of factors influencing the incidence and severity of plaque-induced gingivitis.

Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

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Clinical prediction guides

Clinical features and predictors of osteoarticular manifestations in common variable immunodeficiency.

Ben Khaled M, Merdassi A, Rekaya S, Fraj IB, Lamouchi T, Zaiter I, Kouki R, Bejaoui M, Mellouli F, Ouederni M
Clin Rheumatol 2023 Nov;42(11):3123-3129. Epub 2023 Jul 28 doi: 10.1007/s10067-023-06722-5. PMID: 37505303

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Early Diagnosis of Primary Immunodeficiency Disease Using Clinical Data and Machine Learning.

Neurocysticercosis and HIV/AIDS co-infection: A scoping review.

Jewell PD, Abraham A, Schmidt V, Buell KG, Bustos JA, Garcia HH, Dixon MA, Walker M, Ngowi BJ, Basáñez MG, Winkler AS
Trop Med Int Health 2021 Oct;26(10):1140-1152. Epub 2021 Aug 23 doi: 10.1111/tmi.13652. PMID: 34228854 Free PMC Article

A review of factors influencing the incidence and severity of plaque-induced gingivitis.

Trombelli L, Farina R
Minerva Stomatol 2013 Jun;62(6):207-34. PMID: 23828258

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Recent systematic reviews

The Global, Regional, and National Burden of Adult Lip, Oral, and Pharyngeal Cancer in 204 Countries and Territories: A Systematic Analysis for the Global Burden of Disease Study 2019.

GBD 2019 Lip, Oral, and Pharyngeal Cancer Collaborators, Cunha ARD, Compton K, Xu R, Mishra R, Drangsholt MT, Antunes JLF, Kerr AR, Acheson AR, Lu D, Wallace LE, Kocarnik JM, Fu W, Dean FE, Pennini A, Henrikson HJ, Alam T, Ababneh E, Abd-Elsalam S, Abdoun M, Abidi H, Abubaker Ali H, Abu-Gharbieh E, Adane TD, Addo IY, Ahmad A, Ahmad S, Ahmed Rashid T, Akonde M, Al Hamad H, Alahdab F, Alimohamadi Y, Alipour V, Al-Maweri SA, Alsharif U, Ansari-Moghaddam A, Anwar SL, Anyasodor AE, Arabloo J, Aravkin AY, Aruleba RT, Asaad M, Ashraf T, Athari SS, Attia S, Azadnajafabad S, Azangou-Khyavy M, Badar M, Baghcheghi N, Banach M, Bardhan M, Barqawi HJ, Bashir NZ, Bashiri A, Benzian H, Bernabe E, Bhagat DS, Bhojaraja VS, Bjørge T, Bouaoud S, Braithwaite D, Briko NI, Calina D, Carreras G, Chakraborty PA, Chattu VK, Chaurasia A, Chen MX, Cho WCS, Chu DT, Chukwu IS, Chung E, Cruz-Martins N, Dadras O, Dai X, Dandona L, Dandona R, Daneshpajouhnejad P, Darvishi Cheshmeh Soltani R, Darwesh AM, Debela SA, Derbew Molla M, Dessalegn FN, Dianati-Nasab M, Digesa LE, Dixit SG, Dixit A, Djalalinia S, El Sayed I, El Tantawi M, Enyew DB, Erku DA, Ezzeddini R, Fagbamigbe AF, Falzone L, Fetensa G, Fukumoto T, Gaewkhiew P, Gallus S, Gebrehiwot M, Ghashghaee A, Gill PS, Golechha M, Goleij P, Gomez RS, Gorini G, Guimaraes ALS, Gupta B, Gupta S, Gupta VB, Gupta VK, Haj-Mirzaian A, Halboub ES, Halwani R, Hanif A, Hariyani N, Harorani M, Hasani H, Hassan AM, Hassanipour S, Hassen MB, Hay SI, Hayat K, Herrera-Serna BY, Holla R, Horita N, Hosseinzadeh M, Hussain S, Ilesanmi OS, Ilic IM, Ilic MD, Isola G, Jaiswal A, Jani CT, Javaheri T, Jayarajah U, Jayaram S, Joseph N, Kadashetti V, Kandaswamy E, Karanth SD, Karaye IM, Kauppila JH, Kaur H, Keykhaei M, Khader YS, Khajuria H, Khanali J, Khatib MN, Khayat Kashani HR, Khazeei Tabari MA, Kim MS, Kompani F, Koohestani HR, Kumar GA, Kurmi OP, La Vecchia C, Lal DK, Landires I, Lasrado S, Ledda C, Lee YH, Libra M, Lim SS, Listl S, Lopukhov PD, Mafi AR, Mahumud RA, Malik AA, Mathur MR, Maulud SQ, Meena JK, Mehrabi Nasab E, Mestrovic T, Mirfakhraie R, Misganaw A, Misra S, Mithra P, Mohammad Y, Mohammadi M, Mohammadi E, Mokdad AH, Moni MA, Moraga P, Morrison SD, Mozaffari HR, Mubarik S, Murray CJL, Nair TS, Narasimha Swamy S, Narayana AI, Nassereldine H, Natto ZS, Nayak BP, Negru SM, Nggada HA, Nouraei H, Nuñez-Samudio V, Oancea B, Olagunju AT, Omar Bali A, Padron-Monedero A, Padubidri JR, Pandey A, Pardhan S, Patel J, Pezzani R, Piracha ZZ, Rabiee N, Radhakrishnan V, Radhakrishnan RA, Rahmani AM, Rahmanian V, Rao CR, Rao SJ, Rath GK, Rawaf DL, Rawaf S, Rawassizadeh R, Razeghinia MS, Rezaei N, Rezaei N, Rezaei N, Rezapour A, Riad A, Roberts TJ, Romero-Rodríguez E, Roshandel G, S M, S N C, Saddik B, Saeb MR, Saeed U, Safaei M, Sahebazzamani M, Sahebkar A, Salek Farrokhi A, Samy AM, Santric-Milicevic MM, Sathian B, Satpathy M, Šekerija M, Senthilkumaran S, Seylani A, Shafaat O, Shahsavari HR, Shamsoddin E, Sharew MM, Sharifi-Rad J, Shetty JK, Shivakumar KM, Shobeiri P, Shorofi SA, Shrestha S, Siddappa Malleshappa SK, Singh P, Singh JA, Singh G, Sinha DN, Solomon Y, Suleman M, Suliankatchi Abdulkader R, Taheri Abkenar Y, Talaat IM, Tan KK, Tbakhi A, Thiyagarajan A, Tiyuri A, Tovani-Palone MR, Unnikrishnan B, Vo B, Volovat SR, Wang C, Westerman R, Wickramasinghe ND, Xiao H, Yu C, Yuce D, Yunusa I, Zadnik V, Zare I, Zhang ZJ, Zoladl M, Force LM, Hugo FN
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A systematic review of pregnant women with COVID-19 and their neonates.

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MedGen

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Links from Gene

Immunodeficiency 62(IMD62)

Definition

Clinical features

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Recent systematic reviews

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

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