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Table 1 Expected disease, molecular diagnosis, and potential treatment options for PID patients with diagnoses

From: Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies

Solved European cases
Patient ID Referred from Gender Age Clinical diagnosis/expected disease Mutation inheritance ACMG variant class Mutation(s) identified Treatment options Ref treatment
134.1 Finland Female 4 ADA2 deficiency AR (hom) 5/5 CECR1 p.(R169Q/R169Q) Anti-TNF treatment [40]
1.1 Netherlands Female 50 APECED AR (hom) 5/5 AIRE p.(R257*/R257*)   
217.1 Netherlands Female 23 Chronic granulomatous disease AR (hom) 5/5 NCF2 p.(Y293*/Y293*) * Specific prophylaxis bacterial and fungal (IFN-γ treatment) consider HSCT [43, 44]
70.1 Netherlands Female 27 Ciliary diskinesia AR (hom) 4/4 RSPH9 p.(M1T/M1T) Possibility for lung transplantation due to diagnosis of PCD. [34]
46.1 Finland Female 15 Chronic mucocutaneous candidiasis AD 4 STAT1 p.(Q243E/wt) Ruxolitinib; consider HSCT; IgG replacement therapy [30,31,32]
149.1 Netherlands Female 55 Chronic mucocutaneous candidiasis AD 5 STAT1 p.(Q271P/wt) Ruxolitinib; consider HSCT; IgG replacement therapy [30,31,32]
222.1 Netherlands Male 29 Complement deficiency AR (hom) 5/5 C7 p.(G379R/G379R) * Prophylaxis: vaccination against meningococcus [46]
103.1 Netherlands Male 48 CVID AD 5 NFKB1 p.(S302fs/wt) IgG replacement therapy  
116.1 Netherlands Male 52 CVID AR (hom) 5/5 CECR1 p.(L503fs/L503fs) Anti-TNF treatment [40]
169.1 Netherlands Male 57 CVID, malignancies XL 4 MAGT1 p.(S24*) IgG replacement therapy Mg supplement therapy: Clinical trial NCT02496676 [49]
227.1 Netherlands Male 57 Familial cold autoinflammatory syndrome AD 5 NLRC4 p.(S445P/wt) Anti-IL-1 treatment [53]
32.1 Netherlands Female 11 months Hermansky-Pudlak syndrome AR (CH) 4/4 AP3B1 p.(K59fs/D613fs)   
76.1 Netherlands Female 29 HSV infections AD 5 GATA2 p.(R86fs /wt) HSCT [35]
142.1 Netherlands Female 20 Hyper IgE syndrome AD 5 CFTR p.(W1282*/wt)   
162.1 Netherlands Male 9 IgG deficiency AD 5 TNFRSF13B p.(C104R/wt)   
213.1 Netherlands Male 3 months Interstitial lung disease AR (hom) 4/4 DHFR p.(G21R/G21R) Folinic acid treatment [51]
213.2 Netherlands Female 1 Unknown (affected sibling 213.1) AR (hom) 4/4 DHFR p.(G21R/G21R) Folinic acid treatment [51]
33.1 Netherlands Male 53 Joint, skin, upper respiratory tract infections AD 4 CXCR4 p.(S343fs/wt) Plerixafor; CXCR4 antagonist future treatment option [29]
69.1 Netherlands Male 9 Kabuki syndrome AD 5 KMT2D p.(E5425K/wt)   
29.1 Netherlands Female 28 PAPA syndrome AD 5 PSTPIP1 p.(E250K/wt) Anti-IL-1 treatment [28]
220.1 Netherlands Female 16 Recurrent infections, IFN-γ deficiency AD 4 CARD11 p.(T43P/wt) Glutamine supplementation (IFN-γ treatment) [50]
AD 4 MEFV p.(M680I/wt) Colchicine anti-IL-1 treatment [52]
173.1 Netherlands Female 12 Recurrent urticaria AD 5 NLRP1 p.(L332fs/wt) Anti-IL-1 treatment  
52.1 Netherlands Male 4 Shwachman-Diamond AD 5 TERC n.(37A>G/wt)   
159.1 Finland Male 1 X-linked thrombocytopenia XL 5 WAS p.(V75M) HSCT [39]
Solved Saudi Arabian cases
202.1 Saudi Arabia Female 7 Autoimmune lymphoproliferative syndrome AD 5 CARD11 p.(G123S/wt) Glutamine supplementation; IFN-γ treatment [50]
147.1 Saudi Arabia Female 6 Autoimmune lymphoproliferative syndrome, anti-HCV AR (hom) 4/4 CASP8 p.(A155S/A155S)   
AD 5 CBL c.(1228-2A>G/wt)   
83.1 Saudi Arabia Male 2 Bare lymphocyte syndrome II AR (hom) 5/5 RFXANK p.(D121V/D121V) HSCT [37]
AD 5 INSR p(R145C/wt)   
106.1 Saudi Arabia Male 5 months Bare lymphocyte syndrome II AR (hom) 5/5 RAG1 p.(K186fs/K186fs) HSCT [8]
185.1 Saudi Arabia Female 8 months Bare lymphocyte syndrome II AR (hom) 5/5 RFX5 p.(V378fs/V378fs) HSCT [37]
148.1 Saudi Arabia Male 6 Complement deficiency AR (hom) 5/5 C8A p.(Y210*/Y210*) * Prophylaxis: vaccination against meningococcal disease [46]
129.1 Saudi Arabia Female 8 months Chronic granulomatous disease AR (hom) 5/5 CYBA c.(58+4-7del/58+4-7del) * Specific prophylaxis bacterial and fungal (IFN-γ treatment); consider HSCT [43, 44]
161.1 Saudi Arabia Male 2 Chronic granulomatous disease AR (hom) 5/4 CYBA p.(A117E/A117E) * Specific prophylaxis bacterial and fungal (IFN-γ treatment); consider HSCT [43, 44]
165.1 Saudi Arabia Female 8 Chronic granulomatous disease AR (hom) 5/5 CEBPE p.(R135*/R135*) Consider anti-inflammatory therapy  
168.1 Saudi Arabia Male 3 Chronic granulomatous disease XL 5 CYBB p.(E347fs) * Specific prophylaxis bacterial and fungal (IFN-γ treatment); consider HSCT [43, 44]
156.1 Saudi Arabia Female 3 Congenital neutropenia, myelofibrosis AR (hom) 4/4 VPS45 p.(L410P/L410P) HSCT [47]
113.1 Saudi Arabia Female 13 Dyskeratosis congenita AR (hom) 4/4 WRAP53 p.(R387C/R387C)   
122.1 Saudi Arabia Female 19 Gray platelet syndrome AR (hom) 5/5 ITGA2B p.(R1026W/R1026W)   
126.1 Saudi Arabia Female 11 Hypogammaglobulinemia AR (hom) 5/5 DNMT3B p.(V836M/V836M) Consider HSCT; IgG replacement therapy [41]
127.1 Saudi Arabia Female 10 Hypogammaglobulinemia, bronchiectasis AR (hom) 5/5 ZBTB24 p.(Q498fs/Q498fs) Consider HSCT; IgG replacement therapy [42]
127.2 Saudi Arabia Female 12 Hypogammaglobulinemia AR (hom) 5/5 ZBTB24 p.(Q498fs/Q498fs) Consider HSCT; IgG replacement therapy [42]
138.1 Saudi Arabia Male 1 Hypogammaglobulinemia AR (hom) 5/5 AK2 p.(A182D/A182D) Consider HSCT; IgG replacement therapy [45]
138.2 Saudi Arabia Female 4 Hypogammaglobulinemia AR (hom) 5/5 AK2 p.(A182D/A182D) Consider HSCT; IgG replacement therapy [45]
189.1 Saudi Arabia Female 4 Hypogammaglobulinemia AR (hom) 5/5 DNMT3B p.(V836M/V836M) Consider HSCT; IgG replacement therapy [41]
189.2 Saudi Arabia Male 1 Hypogammaglobulinemia AR (hom) 5/5 DNMT3B p.(V836M/V836M) Consider HSCT; IgG replacement therapy [41]
196.1 Saudi Arabia Male 7 Hypogammaglobulinemia AR (hom) 5/5 DNMT3B p.(V836M/V836M) Consider HSCT; IgG replacement therapy [41]
198.1 Saudi Arabia Male 2 Hypogammaglobulinemia AR (hom) 5/5 JAK3 p.(R403H/R403H) HSCT [8]
204.1 Saudi Arabia Male 6 months Hypogammaglobulinemia AR (hom) 5/5 DNMT3B p.(V836M/V836M) Consider HSCT; IgG replacement therapy [41]
100.1 Saudi Arabia Female 8 IgG deficiency AD 5 PIK3R1 c.(1425+1G>T/ wt) IgG replacement therapy [38]
186.1 Saudi Arabia Male 6 Microcytic anemia AD 4 HBB p.(Q7V/wt)   
236.1 Saudi Arabia Male 6 Non-immune hemolytic anemia XL 5 G6PD p.(V461G) * Dietary: Avoidance of fava beans and specific drugs [54]
240.1 Saudi Arabia Female 2 months Pancytopenia AR (hom) 5/5 MTHFD1 p.(R173C/R173C) Folic acid and folinic acid treatment [51]
94.1 Saudi Arabia Female 8 Pancytopenia, hyper- and hypogammaglobulinemia AR (CH) 5/3 FANCA p.(L910fs/C1142Y)   
114.1 Saudi Arabia Female 8 months SCID AR (hom) 4/4 DCLRE1C p.(P117Q/P117Q) Consider HSCT [8]
115.1 Saudi Arabia Female 8 months SCID AR (hom) 4/4 ZAP70 p.(S524C/S524C) HSCT [8]
105.1 Saudi Arabia Male 5 months SCID, HLH XL 5 IL2RG p.(I273fs) Consider HSCT, IgG replacement therapy [8]
112.1 Saudi Arabia Male 8 months SCID, Omenn syndrome AR (hom) 5/5 RAG1 p.(K186fs/K186fs) HSCT [8]
146.1 Saudi Arabia Male 11 months SCID, HLH AR (hom) 5/5 JAK3 Ex10 Deletion HSCT [8]
154.1 Saudi Arabia Male 3 months SCID, BCGitis AR (hom) 4/4 RAG2 p.(K106E/K106E) HSCT [8]
199.1 Saudi Arabia Male 3 SCID, Burkitt’s lymphoma AR (hom) 4/4 LCK p.(R480fs/R480fs) HSCT [8]
84.1 Saudi Arabia Male 9 Severe eczema AD 4 SAMHD1 p.(F329fs/wt) Consider anti-IL-5 or anti-IL4R treatment  
61.1 Saudi Arabia Female 12 Severe infections, pancytopenia AD 4 CTLA4 p.(G146R /wt) Abatacept (recombinant CTLA4) [33]
82.1 Saudi Arabia Female 4 Severe infections, thrombocytopenia AR (hom) 5/5 LRBA p.(T1587fs/T1587fs) Abatacept (recombinant CTLA4) [36]
190.1 Saudi Arabia Male 4 Severe lung infections AR (hom) 5/5 AK2 p.(A182D/A182D) Consider HSCT; IgG replacement therapy [45]
145.1 Saudi Arabia Female 5 months Severe infections, hypergammaglobulinemia AR (hom) 5/5 CFTR c.(579+1G>A/579+1G>A)   
239.1 Saudi Arabia Female 4 months Severe infections, hemolytic anemia AD 4 ANK1 p.(Q1313*/wt)   
242.1 Saudi Arabia Female 4 Severe infections, leukocytosis, hypergammaglobulinemia AD 5 STAT3 p.(V713M/wt) * Specific prophylaxis bacterial and fungal (IFN-γ treatment) [32]
160.1 Saudi Arabia Female 2 Shwachman-Diamond, CD3 deficiency AR (hom) 4/4 PRF1 p.(R410P/R410P) Possible T cell gene therapy (under development) [48]
153.1 Saudi Arabia Male 15 T cell acute lymphoblastic leukemia AR (hom) 5/5 NBN p.(Y197fs/Y197fs)   
AD 4 RPL5 p.(G140S/wt)   
107.1 Saudi Arabia Male 21 Thrombocytopenia XL 5 WAS p.(T48A) HSCT [39]
188.1 Saudi Arabia Male 6 months TORCH AR (hom) 4/4‡ RNASEH2B p.(D119G/D119G)   
195.1 Saudi Arabia Male 1 months Transaldolase deficiency AR (hom) 5/5 TALDO1 p.(Q265fs/Q265fs)   
193.1 Saudi Arabia Male 38 Viral infections, autoimmune manifestations, thrombocytopenia AR (hom) 5/5 C7 p.(G378R/G378R) * Prophylaxis: vaccination against meningococcus [46]
  1. Table 1 lists clinical diagnoses and identified pathogenic or likely pathogenic genetic mutations in all 72 patients from Europe and Saudi Arabia. In addition, the table provides potential therapeutic options resulting from identification of the molecular defect
  2. AD autosomal dominant, APECED autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, AR autosomal recessive, CH compound heterozygous, CVID common variable immune deficiency, HSCT hematopoietic stem cell transplantation, HLH hemophagocytic lymphohistiocytosis, hom homozygous, IFN-γ interferon- γ, IL-1 interleukin-1, IgG immunoglobulin G, PCD primary ciliary dyskinesia, SCID severe combined immunodeficiency, TNF tumor necrosis factor, TORCH toxoplasmosis, other, rubella, cytomegalovirus, and herpes simplex infections, XL X-linked
  3. *Indirect measures or prophylaxis