Comprehensive mutation screening for 10 genes in Chinese patients suffering very early onset inflammatory bowel disease

Table 1 Genotypes of 13 patients diagnosed with very early-onset inflammatory bowel disease

Patient	Gene	Variation	Homo/Heterozygote	Function defect
1	IL-10RA	p.R101W	Homozygote	Yes
2	IL-10RA	p.R101W	Compound heterozygote	Yes
		p.V100G (novel mutation)		Pathogenic supporting by Polyphen 2 and SIFT
3	IL-10RA	p.R101W	Compound heterozygote	Yes
		p.Y64C (novel mutation)		Pathogenic supporting by Polyphen 2 and SIFT
4	IL-10RA	p.R117H (rs199989396)	Heterozygote	Yes
	NOD2	p.R703C (rs5743277)	Heterozygote	Susceptibility to CD recorded in HGMD
	FUT2	p.I140F (rs1047781)	Heterozygote	Susceptibility to CD in Chinese population reported by Hu et al[31]
5	IL-10RB	p.K47E (rs2834167)	Homozygote	SNP in a VEO-UC child reported by Galatola et al[29]
		p.E141K (rs387907326)	Heterozygote	Pathogenic supporting by Polyphen 2 and SIFT
	IL-10RA	p.P115P (rs22280554)	Homozygote	Susceptibility to VEO-IBD reported by Moran et al[30]
		p.I224V (rs22280555)	Homozygote
	FUT2	p.I140F (rs1047781)	Heterozygote	Susceptibility to CD in Chinese population reported by Hu et al[31]
6	IL-10RA	p.P115P (rs22280554)	Homozygote	Susceptibility to VEO-IBD reported by Moran et al[30]
		p.I224V (rs22280555)	Homozygote
	FUT2	p.I140F (rs1047781)	Homozygote	Susceptibility to CD in Chinese population reported by Hu et al[31]
7	IL-10RA	p.P115P (rs22280554)	Homozygote	Susceptibility to VEO-IBD reported by Moran et al[30]
		p.I224V (rs22280555)	Homozygote
	FUT2	p.I140F (rs1047781)	Heterozygote	Susceptibility to CD in Chinese population reported by Hu et al[31]
8	IL-10RB	p.K47E (rs2834167)	Homozygote	SNP in a VEO-UC child reported by Galatola et al[29]
	FUT2	p.I140F (rs1047781)	Heterozygote	Susceptibility to CD in Chinese population reported by Hu et al[31]
9	IL-10RB	p.K47E (rs2834167)	Heterozygote	SNP in a VEO-UC child reported by Galatola et al[29]
	FUT2	p.I140F (rs1047781)	Heterozygote	Susceptibility to CD in Chinese population reported by Hu et al[31]

Patients 10, 11, 12 and 13 were wild types in all these genes. CD: Crohn's disease; UC: Ulcerative colitis; VEO-IBD: Very early-onset inflammatory bowel disease; VEO-UC: Very early-onset ulcerative colitis; SNP: Single nucleotide polymorphism; HGMD: The Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/ac/index.php).

Table 2 Clinical manifestations of very early-onset inflammatory bowel disease

	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5	Patient 6	Patient 7	Patient 8	Patient 9	Patient 10	Patient 11	Patient 12	Patient 13
Gender	F	M	M	M	M	M	M	M	M	M	M	F	F
Age of onset (mo)	8	1	0.3	0.3	4	0.2	9	2	0.5	3	0.7	10	36
Height percentile	19%	1%	3%	1%	1%	1%	52%	1%	15%	1%	19%	16%	20%
Weight percentile	1%	1%	1%	1%	1%	20%	55%	13%	8%	15%	16%	60%	33%
Diarrhea (times/d)	> 10	7-8	> 10	10	5-10	5-6	7-8	2-4	7-8	No diarrhea	7-8	No diarrhea	2-3
Bloody stool	+	+	+	+	+	-	+	+	+	-	+	+	+
Infection	Sepsis	Pneumonia	No	Pneumonia, Clostridium difficile infection	Sepsis, oral candidiasis, fungemia, Clostridium difficile infection	Recurrent respiratory infection	No	No	No	Repeated fever of unknow origin	Oral candidiasis, gingivitis	No	No
Perianal lesion	Fistulae	No	No	Excrescence	Fistulae, abscess, excrescence	Fistulae, ulcer	No	No	No	No	Fistulae, abscess, excrescence	No	No
Clinical diagnosis	CD	CD	CD	CD	CD	CD	CD	CD	UC	CD	CD	UC	UC
Medication	GC, 6-MP	IFX, THD	GC, THD	GC, IFX1, THD	GC, IFX, THD	GC, IFX1	GC, IFX, MES	GC, IFX1, THD, 6-MP	GC, MES	GC, 6-MP, THD	GC, IFX, THD, 6-MP	MES	GC, MES
Clinical status	NR	PR	Died at 2 yr because of severe sepsis	PR	Died at 3 yr because of intestinal failure	NR	CR	PR	CR	CR	PR	CR	CR

¹Allergic to IFX. CD: Crohn's disease; UC: Ulcerative colitis; GC: Glucocorticoid; 6-MP: 6-mercaptopurine; IFX: Infliximab; THD: Thalidomide; MES: Mesalazine; NR: Non-remission; PR: Partial remission; CR: Complete remission.

Table 3 Comparison of features between patients with mutations and polymorphisms

	Group 1	Group 2
Size of sample	5	8
Age of onset (mo)	2.7	7.7
Height percentile	5.0%	15.6%
Weight percentilea	1.0%	27.5%
WBC (× 10-9)	15.2	16.3
Hemoglobin (g/L)a	87.4	108.5
Platelets (× 10-9)	538.4	424.0
C reactive protein (mg/L)	60.7	35.9
ESR (mm/H)	32.2	16.6
TNFα (pg/mL)	44.5	51.6
Diagnosis of CD	100.0%	62.5%
Recurrent infection	80.0%	25.0%
Perianal disease	60.0%	25.0%

^aP < 0.05. All measurement data are expressed as mean. Group 1: Mutations in IL-10RA or IL-10RB; Group 2: Polymorphisms. Height and weight percentile was calculated according to WHO charts. WBC: White blood cell; ESR: Erythrocyte sedimentation rate; TNFα: Tumor necrosis factor alpha; CD: Crohn's disease.