Potential protein–phenotype correlation in three lipopolysaccharide-responsive beige-like anchor protein-deficient patients

Table 1 Clinical features of the three patients with LPS-responsive beige-like anchor protein deficiency

		Patient 1	Patient 2	Patient 3
Age of onset		2.0 yr	10.0 mo	< 1.0 yr
Age of genetic diagnosis (yr)		3.9	2	3
Current age (yr)		5.4	7.1	3.2
Sex		M	F	M
Consanguinity		No	No	No
Final outcome		Alive	Alive	Alive
First symptoms		Diarrheal, abdominal distention	Diarrheal, hematochezia, abdomen pain	Diarrheal, growth delay
Failure to thrive		(+)	(-)	(+)
Other clinical findings		RURI, temporary hypothyroidism, neutropenia, urticaria, arthritis, growth delay	No	Elevated liver enzymes, renal pelvis separation, sepsis, temporary hypothyroidism, pneumonia
Endoscopy findings		Non-specific colitis	Chron's-like disease	Non-specific colitis
Infectious agents		No documented infectious agent	No documented infectious agent	Rotavirus, Klebsiella pneumoniae, Bacillus thuringiensis
IgG (g/L) (RV: 4.95-12.85)		12.7	8.7	4.4
IgA (g/L) (RV: 0.52-2.16)		1.42	0.28	0.49
IgM (g/L) (RV: 0.65-2.01)		0.8	1.01	2.04
White blood cells count (× 109)		2.70-3.60	7.2	9.7
(RV: 4.0-10.0)
Absolute lymphocyte count (× 109) (RV: 1.20-4.00)		2.00-2.80	3.6	3.36
Absolute neutrophil count (× 109) (RV: 2.00-7.00)		0.21-0.42	3.18	5.54
CD19+ B cells	(%) (RV: 14-21)	12.78	18.63	12.03
	Count	345.82	535.9	349.8
CD3+ T cells	(%) (RV: 64-73)	76.97	69.66	59.69
	Count	2083.5	2003.7	1735.4
CD3+CD4+ Th cells	(%) (RV: 29-36)	39.86	37.37	33.32
	Count	1078.83	1074.84	965.76
CD3+CD8+ Tc cells	(%) (RV: 24-34)	32.04	31.4	24.38
	Count	867.33	903.31	708.84
CD3-CD16+56+NK cells	(%) (RV: 11-23)	8.88	10.34	26.98
	Count	240.5	297.45	784.43
CD4/CD8		1.24	1.19	1.36
Immunosuppressive agents		/	Steroids, 5-ASA, AZA	Steroids
HSCT		+	-	-

RURI: Recurrent upper respiratory infections; RV: Reference values; ASA: Acetyl salicylic acid; AZA: Azathioprine; HSCT: Hematopoietic stem cell transplantation.

Table 2 LPS-responsive beige-like anchor mutations reported in patients

Patient	Ethnicity	CF	Affected exon/intron	Defect (cDNA)	Defect (protein)
P1[2,7]	Arab	Y	Exon 44	c.6657_6658del	p.E2219Dfs*3
P2[2,7]	Arab	Y	Exon 44	c.6657_6658del	p.E2219Dfs*3
P3 [2,7]	Arab	Y	Exon 44	c.6657_6658del	p.E2219Dfs*3
P4[2,7]	Arab	Y	Exon 44	c.6657_6658del	p.E2219Dfs*3
P5[2,7]	Arab	Y	Exon 44	c.6657_6658del	p.E2219Dfs*3
P6[2,6]	Sicilian	Y	Exon 30	c.5047C>T	p.R1683*
P7[2,6]	Iranian	Y	Exon 2	c.175G>T	p.E59*
P8[2,6,18]	Iranian	Y	Exons 1-2	c.A1-G216del	p.M1-L72del
P9[2,8]	Pakistani	Y	Exons 1-30	c.A1-G5171del	p.M1-R1724del
P10[2,9]	Arabian	Y	Exon 16	c.2032C>T	p.Q678*
P11[2,9]	Lebanese	Y	Exon 7	c.865_866delTG	p.V290Efs*3
P12[2,19]	Kurdish	Y	Exon 48	c.7162_7162delA	p.T2388Pfs*8
P13[2,19]	Kurdish	Y	Exon 48	c.7162_7162delA	p.T2388Pfs*8
P14[2,20,21]	Turkish	Y	Exon 57; Exon 57	c.A8470C; p.T8471C	p.I2824L; p.I2824T
P15[2]	NA	Y	Exon 33	c.5505_5505delT	p.I1836*
P16[2]	North African	Y	Exon 44	c.6607C>T	p.R2203*
P17[2]	Iranian	Y	Introns 8-9	c.1014 + 1 C> T
P18[2,12,14,22]	Iranian	Y	Exon 30	c.C4814G	p.S1605*
P19[2]	Iranian	Y	Exon 4	c.C544T	p.R182*
P20[2,12,14,22]	Iranian	Y	Intron 29-30	c.4729 + 2insA
P21[11]	Libyan	Y	Exon 20	c.2445_2447delinsCC	p.P816Lfs*4
P22[11]	Libyan	Y	Exon 20	c.2445_2447delinsCC	p.P816Lfs*4
P23[23]	Persian	Y	Exon 6	c.743_744insAAGA	p.D248Efs*3
P24[24]	Turkish	Y	Exon 48	c.7162delA	p.T2388Pfs*8
P25[25]	Egyptian	Y	Exon 46	c.6862delT	p.Y2288Mfs*29
P26[21,26]	Turkish	Y	Exon 33	c.5505delT	p.I1836*
P27[27]	Caucasian	NA	Exon 23; Exon 54	c.3647_3650delCTAA; c.7937T>G	p.N1217Sfs*7; p.I2646S
P28[28]	Omani	Y	Exon 23	c.3811C>T	p.R1271*
P29[9,30]	Turkish	N	Exon 23; Exon 54	c.3156_3156delT; c.7976C>A	p.D1053Tfs*2; p.S2659*
P30[16,21]	Turkish	Y	Exon 6	c.675G > A	p.W225*
P31[30]	Moroccan	Y	Exon 47	c.7042C>T	p.R2348*
P32[30]	Moroccan	Y	Exon 47	c.7042C>T	p.R2348*
P33[30]	Omani	Y	Intron 34-35	c.5581-1G>A
P34[30]	Egyptian	Y	Exon 20	c.2447_2447delC	p.P816Lfs*4
P35[30]	Chinese	N	Intron 29-30	c.(4729+1_4730-1)_(5171+1_5172-1)del
P36[22]	Pakistani	Y	Exon 24	c.3988delinsAA	p.I1330Nfs*18
P37[31]	Caucasian	Y	Exon 23	c.2836_2839delGAAA	p.E946*
P38[32]	Arab	Y	Exon 54	c.7970T>G	p.I2657S
P39[32]	Arab	Y	Exon 56	c.8174_8175insCATG	p.N2727Hfs*13
P40[32]	Arab	Y	Exon 53	c.7869_7873delTTCTA	p.S2624Rfs*23
P41[13]	Belarusian	N	Exon 22	c.2762C>G	p.S921*
P42[13]	Belarusian	N	Exon 22	c.2762C>G	p.S921*
P43[33]	NA	Y	Exon 21	c.2496C>A	p.C832*
P44[33]	NA	Y	Exon 21	c.2496C>A	p.C832*
P45[34]	NA	NA	NA	c.2450+1C >T	p.E789fs*792
P46[35]	Moroccan	Y	Intron 20-21	c.2450-3C>A
P47[36]	NA	NA	Exon 15	c.1931delinsCC	p.R645Afs*3
P48[37]	Caucasian	N	Exon 23	c.3366delinsAA	p. A1123Sfs*2
P49[38]	Arab	Y	Intron 41-42	c.6364-1G >C
P50[16,39]	Turkish	Y	Exon 34	c.5527delT	p.C1843Afs*2
P51[16,39]	Turkish	Y	Exon 47	c.7042C>T	p.R2348*
P52[16]	NA	Y	Exon 47	c.7041G>T	p.W2347C
P53[16]	NA	Y	Intron 6–7	IVS6+1delT
P54[16]	NA	Y	Exon 31	c.5504delT	L1835fs*1
P55[21,32]	Turkish	Y	Exon 23	c.2893_2900delinsGCCAGATATATATATATATATATATATA	p.I964Afs*32
P56[16]	NA	Y	Exon 2	c.175G>T	p.E59*
P657[16]	NA	Y	Exon 23	c.2836_2839delGAAA	p.E946*
P58[2,6]	Arab	Y	Exon 54	c.7970T>G	p.I2657S
P59[2,6]	Arab	Y	Exon 54	c.7970T>G	p.I2657S
P60[2,9]	Lebanese	Y	Exon 7	c.865_866delTG	p.V290Efs*3
P61[2,32,40]	Arab	Y	Exon 54	c.7970T>G	p.I2657S
P62[2,32,40]	Arab	Y	Exon 56	c.8174_8175insCATG	p.N2727Hfs*13
P63[2,32,40]	Arab	Y	Exon 56	c.8174_8175insCATG	p.N2727Hfs*13
P64[2,12,14,22]	Iranian	Y	Exon 30	c.C4814G	p.S1605*
P65[2]	Lebanese	Y	Exon 23	c.2963_2963delA	p.N988Mfs*8
P66[2,12,14]	Iranian	Y	Intron 29-30	c.4729+4dupA
P67[41]	NA	Y	Exon 51	c.7620_7621insT	p.A2541Cfs*2
P68[41]	NA	Y	Exon 51	c.7620_7621insT	p.A2541Cfs*2
P69[25]	Egyptian	Y	Exon 46	c.6862delT	p.Y2288Mfs*29
P70[21]	Turkish	N	Exon 23; Exon 54	c.3028G>A; c.7976G > C	p.Q1010*; p.S2659*
P71[30]	Omani	Y	Exon 23	c.3811C>T	p.R1271*
P72[30]	Iranian	Y	Exon 14	c.1764delinsTT	p.M589Yfs*18
P73[22]	Turkish	Y	Intron 30-31	c.5172-2A>G
P74[32]	Arab	Y	Exon 54	c.7970T>G	p.I2657S
P75[32]	Arab	Y	Exon 54	c.7970T>G	p.I2657S
P76[16]	Turkish	N	Exon 37; Exon 47	c.5805delT; c.7042C>T	p.C1935Wfs*4; p.R2348*
P77[16]	NA	Y	Exon 23	c.3396_3397delCA	p.N1132Lfs*8
P78[16]	Turkish	Y	Exon 47	c.7042C>T	p.R2348*
P79[16]	NA	Y	Exon 23	c.3811C>T	p.R1271*
P80[16]	NA	Y	Exon 3; Exon 4	c.(501+1_502-1)_(733+1_734-1)del	P. G75_W183*
P81[42]	Chinese	NA	Exon 57; Exon 25	c.8436G>C; c.4089A>T	p.K2812N; p.Q1363H
P82[43]	Chinese	N	Exon 15; Exon 29	c.1933C>T; c.G4570-G4729del	p.R645*; p.E1524-S1576 del
P83[43]	Chinese	N	Exon 23; Exon 12	c.3778G>C; c.1570G>A	p.A1260P; p.G524S
P84our patient	Chinese	N	Exon 8; Exon 53	c.918delC; c.C7727-G7882	p.H306Qfs*;15; p.A2576-T2627 del
P85our patient	Chinese	N	Exon 12	c.1570G>A	p.524G>S
P86our patient	Chinese	N	Exon 21	c.2479C>T	p.Arg827*

P: Patient; CF: Consanguineous family; Y: Yes; N: No; NA: Not available.