Table 1.
The clinical spectrum of patients with PKCδ deficiency
KindredPatientMutation (predicted protein variant)OriginSexFollow-upAge at onset of symptomsAutoimmune manifestationsBCG status; clinical infectious phenotype (infections, microbiology, pathology results); treatment, prophylaxisReference
P1 c.1840C>T/c.1840C>T (p.R614W/p.R614W) Mexico, living in USA Alive 3 yr Autoimmune hemolytic anemia, SLE ANA+, anti-RNP+, anti-smith+, anti-SSA+ BCG-vaccine: no AE; recurrent pneumonia, EBV infection, recurrent otitis media; corticosteroids, rapamycin; prophylaxis: NR Kuehn et al., 2013  
P2 c.742G>A/c.742G>A (p.G248S/p.G248S) Turkey Alive 1 yr SLE ANA+ BCG-vaccine: no AE; recurrent pneumonia, CMV infection, recurrent gastroenteritis; hydroxychloroquine; prophylaxis: IVIG, antibiotics Kiykim et al., 2015  
P3 c.1528G>A/c.1528G>A (p.G510S/p.G510S) France Alive 10 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; severe Legionella pneumonia, recurrent pneumonia, severe papillomatosis; corticosteroids, hydroxychloroquine; prophylaxis: NR Belot et al., 2013  
P4 c.1528G>A/c.1528G>A (p.G510S/p.G510S) Dead 3 yr Autoimmune hemolytic anemia, SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; died at age 13 yr from septic shock due to P. aeruginosa; corticosteroids, MMF, anti-CD20 (rituximab); prophylaxis: NR 
P5 c.1528G>A/c.1528G>A (p.G510S/p.G510S) Alive 6 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; pleuritis and recurrent pneumonia; corticosteroids, MMF; prophylaxis: IVIG 
P6 c.1352+1G>A/c.1352+1G>A (?/?) Turkey Alive 1 yr SLE ANA+, anti-dsDNA+, anti-cardiolipin+ BCG-vaccine: no AE; recurrent pneumonia, urinary tract infections, recurrent gastroenteritis, recurrent otitis media; corticosteroids, anti-CD20 (rituximab); prophylaxis: IVIG, antibiotics Salzer et al., 2013  
P7 c.1294G>T/c.1294G>T (p.G432W/p.G432W) Pakistan, living in UK Alive 1 yr Autoimmune hemolytic anemia, SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; corticosteroids, anti-CD20 (rituximab), azathioprine; prophylaxis: IVIG Lei et al., 2018; Nanthapisal et al., 2017  
P8 c.1294G>T/c.1294G>T (p.G432W/p.G432W) Alive 1 yr Autoimmune hemolytic anemia, SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; cervical and inguinal lymphadenopathy; corticosteroids, anti-CD20 (rituximab), azathioprine; prophylaxis: IVIG 
P9 c.1294G>T/c.1294G>T (p.G432W/p.G432W) Alive 2 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; corticosteroids, anti-CD20 (ofatumumab); prophylaxis: IVIG 
P10 c.788-2A>G/c.571C>T (?/p.Q191*) UK Alive 9 mo SLE ANA+ BCG-vaccine: no AE; Listeria meningitis, recurrent otitis media, early-onset enterocolitis, systemic Candida infection, sepsis due to E. faecium, recurrent A. xyloxidans cervical lymphadenitis, SARS-CoV-2 infection; sirolimus, anti-CD20 (rituximab); prophylaxis: IVIG Unpublished data; Meyts et al., 2021  
P11 c.788-2A>G/c.571C>T (?/p.Q191*) Alive 6 mo SLE ANA+ BCG-vaccine: no AE; H. influenzae sepsis, recurrent gastroenteritis, early-onset enterocolitis; MMF, anti-CD20 (rituximab); prophylaxis: IVIG 
P12 c.1293_1294insA/ c.1293_1294insA (p.G432Rfs*15/p.G432Rfs*15) Afghanistan, living in Iran Alive 1 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; S. pneumoniae pneumonia, H. influenza otitis media, recurrent oral candidiasis, recurrent pneumonia, recurrent gastroenteritis; corticosteroids, NSAIDs, azathioprine; prophylaxis: cyclic rotation of sulfamethoxazole-trimethoprim/amoxicillin and azithromycin Sharifinejad et al., 2020  
P13 c.571+2dup/c.571+2dup (?/?) Turkey Alive 1 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: at 2 mo of age, BCG-osis; Salmonella bacteremia; S. aureus inguinal lymphadenitis, recurrent gingivitis; antimycobacterial treatment, ceftriaxone; corticosteroids; prophylaxis: amoxicillin, IVIG This paper 
P14 c.1384C>T/c.1384C>T (p.Q462*/p.Q462*) Turkey Alive 7 mo Autoimmune hemolytic anemia, ANA+ BCG-vaccine: BCG-itis; recurrent gastroenteritis; isoniazid, rifampicin; corticosteroids; prophylaxis: none at present This paper 
P15 c.1384C>T/c.1384C>T (p.Q462*/p.Q462*) Alive 7 mo Autoimmune hemolytic anemia, ANA+ BCG vaccine: BCG-itis; recurrent gastroenteritis, shingles; isoniazid, rifampicin; corticosteroids; prophylaxis: IVIG 
P16 c.642del/c.642del (p.N214Kfs*26/p.N214Kfs*26) Iran Alive 1 yr No SLE, ANA, anti-dsDNA BCG vaccine: BCG-itis; isoniazid, rifampicin, azithromycin; prophylaxis: none at present This paper 
P17 c.642del/c.642del (p.N214Kfs*26/p.N214Kfs*26) Alive No SLE, ANA, anti-dsDNA BCG vaccine: no AE; asymptomatic; prophylaxis: none at present 
KindredPatientMutation (predicted protein variant)OriginSexFollow-upAge at onset of symptomsAutoimmune manifestationsBCG status; clinical infectious phenotype (infections, microbiology, pathology results); treatment, prophylaxisReference
P1 c.1840C>T/c.1840C>T (p.R614W/p.R614W) Mexico, living in USA Alive 3 yr Autoimmune hemolytic anemia, SLE ANA+, anti-RNP+, anti-smith+, anti-SSA+ BCG-vaccine: no AE; recurrent pneumonia, EBV infection, recurrent otitis media; corticosteroids, rapamycin; prophylaxis: NR Kuehn et al., 2013  
P2 c.742G>A/c.742G>A (p.G248S/p.G248S) Turkey Alive 1 yr SLE ANA+ BCG-vaccine: no AE; recurrent pneumonia, CMV infection, recurrent gastroenteritis; hydroxychloroquine; prophylaxis: IVIG, antibiotics Kiykim et al., 2015  
P3 c.1528G>A/c.1528G>A (p.G510S/p.G510S) France Alive 10 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; severe Legionella pneumonia, recurrent pneumonia, severe papillomatosis; corticosteroids, hydroxychloroquine; prophylaxis: NR Belot et al., 2013  
P4 c.1528G>A/c.1528G>A (p.G510S/p.G510S) Dead 3 yr Autoimmune hemolytic anemia, SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; died at age 13 yr from septic shock due to P. aeruginosa; corticosteroids, MMF, anti-CD20 (rituximab); prophylaxis: NR 
P5 c.1528G>A/c.1528G>A (p.G510S/p.G510S) Alive 6 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; pleuritis and recurrent pneumonia; corticosteroids, MMF; prophylaxis: IVIG 
P6 c.1352+1G>A/c.1352+1G>A (?/?) Turkey Alive 1 yr SLE ANA+, anti-dsDNA+, anti-cardiolipin+ BCG-vaccine: no AE; recurrent pneumonia, urinary tract infections, recurrent gastroenteritis, recurrent otitis media; corticosteroids, anti-CD20 (rituximab); prophylaxis: IVIG, antibiotics Salzer et al., 2013  
P7 c.1294G>T/c.1294G>T (p.G432W/p.G432W) Pakistan, living in UK Alive 1 yr Autoimmune hemolytic anemia, SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; corticosteroids, anti-CD20 (rituximab), azathioprine; prophylaxis: IVIG Lei et al., 2018; Nanthapisal et al., 2017  
P8 c.1294G>T/c.1294G>T (p.G432W/p.G432W) Alive 1 yr Autoimmune hemolytic anemia, SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; cervical and inguinal lymphadenopathy; corticosteroids, anti-CD20 (rituximab), azathioprine; prophylaxis: IVIG 
P9 c.1294G>T/c.1294G>T (p.G432W/p.G432W) Alive 2 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; corticosteroids, anti-CD20 (ofatumumab); prophylaxis: IVIG 
P10 c.788-2A>G/c.571C>T (?/p.Q191*) UK Alive 9 mo SLE ANA+ BCG-vaccine: no AE; Listeria meningitis, recurrent otitis media, early-onset enterocolitis, systemic Candida infection, sepsis due to E. faecium, recurrent A. xyloxidans cervical lymphadenitis, SARS-CoV-2 infection; sirolimus, anti-CD20 (rituximab); prophylaxis: IVIG Unpublished data; Meyts et al., 2021  
P11 c.788-2A>G/c.571C>T (?/p.Q191*) Alive 6 mo SLE ANA+ BCG-vaccine: no AE; H. influenzae sepsis, recurrent gastroenteritis, early-onset enterocolitis; MMF, anti-CD20 (rituximab); prophylaxis: IVIG 
P12 c.1293_1294insA/ c.1293_1294insA (p.G432Rfs*15/p.G432Rfs*15) Afghanistan, living in Iran Alive 1 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: no AE; S. pneumoniae pneumonia, H. influenza otitis media, recurrent oral candidiasis, recurrent pneumonia, recurrent gastroenteritis; corticosteroids, NSAIDs, azathioprine; prophylaxis: cyclic rotation of sulfamethoxazole-trimethoprim/amoxicillin and azithromycin Sharifinejad et al., 2020  
P13 c.571+2dup/c.571+2dup (?/?) Turkey Alive 1 yr SLE ANA+, anti-dsDNA+ BCG-vaccine: at 2 mo of age, BCG-osis; Salmonella bacteremia; S. aureus inguinal lymphadenitis, recurrent gingivitis; antimycobacterial treatment, ceftriaxone; corticosteroids; prophylaxis: amoxicillin, IVIG This paper 
P14 c.1384C>T/c.1384C>T (p.Q462*/p.Q462*) Turkey Alive 7 mo Autoimmune hemolytic anemia, ANA+ BCG-vaccine: BCG-itis; recurrent gastroenteritis; isoniazid, rifampicin; corticosteroids; prophylaxis: none at present This paper 
P15 c.1384C>T/c.1384C>T (p.Q462*/p.Q462*) Alive 7 mo Autoimmune hemolytic anemia, ANA+ BCG vaccine: BCG-itis; recurrent gastroenteritis, shingles; isoniazid, rifampicin; corticosteroids; prophylaxis: IVIG 
P16 c.642del/c.642del (p.N214Kfs*26/p.N214Kfs*26) Iran Alive 1 yr No SLE, ANA, anti-dsDNA BCG vaccine: BCG-itis; isoniazid, rifampicin, azithromycin; prophylaxis: none at present This paper 
P17 c.642del/c.642del (p.N214Kfs*26/p.N214Kfs*26) Alive No SLE, ANA, anti-dsDNA BCG vaccine: no AE; asymptomatic; prophylaxis: none at present 

Family code, patient number, and mutations are as in Fig. 1. Predicted protein variations are indicated in parenthesis. ? indicates unknown prediction of splice site variants. Patient origin, sex, current vital status, age at onset of symptoms, and clinical phenotypes are shown. AE, adverse effect; F, female; M, male; NR, not reported; NSAID, nonsteroidal anti-inflammatory drug.

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