Clinical utility of genomic investigations in a Middle Eastern pediatric gastroenterology disease cohort

Table 1 Summary of positive genetic testing results and detected variants in the study cohort

ID	Primary indication	Technology used	Test done	Variants	Inheritance	Zygosity	Classification
6	Very early onset IBD	NGS	WESTRIO	NM_000377.3(WAS):c.383T>C; p.(Phe128Ser)	X-linked recessive	Hemizygous	LP
14	Very early onset IBD	CMA	CMA	Xp21.1p11.4 (CYBB gene) deletion 1.83 Mb	X-linked recessive	Hemizygous	Pathogenic
15	Recurrent peri-anal abscess	CMA	CMA	Xp21.1p11.4 (CYBB gene) deletion 1.83 Mb	X-linked recessive	Hemizygous	Pathogenic
16	Very early onset IBD	NGS	WES	TTC7A: NM_020458.4, c.133_166del (p.Gly45SerfsTer23)	AR	Heterozygous	LP
17	Liver failure and direct hyperbilirubinemia	NGS	Custom gene panel	NM_002437.5(MPV17):c.280G>C; p.(Gly94Arg)	AR	Homozygous	LP
19	Direct hyperbilirubinemia, multiple congenital anomalies	CMA	CMA	arr[GRCh37] 18p11.32q23(136,227_78,014,123)x3	Chromosomal disorder	-	Pathogenic
20	Persistent indirect hyperbilirubinemia	NGS	UGT1A1 full gene sequencing	NM_000463.3(UGT1A1):c.625C>T; p.(Arg209Trp) NM_000463.3(UGT1A1): C.-41_-40dupTA; p.?	AR AR	Homozygous homozygous	Pathogenic LP
21	Persistent indirect hyperbilirubinemia	NGS	Cholestasis panel	NM_000463.3(UGT1A1): C.-41_-40dupTA; p.?	AR	Homozygous	Pathogenic
23	Persistent indirect hyperbilirubinemia	NGS	Cholestasis panel	NM_005603.4(ATP8B1):c.3040C>T; p.(Arg1014*)	AR	Homozygous	Pathogenic
24	Persistent indirect hyperbilirubinemia	NGS	Cholestasis panel	NM_000463.2(UGT1A1): C.1021C>T; p.R341*	AR	Homozygous	Pathogenic
25	Persistent elevated liver enzymes, congenital heart anomalies	NGS	Alagile syndrome	NM_000214.2(JAG1): C.1052delG; p.(Cys351 Leufs*61)	AD	Heterozgous	Pathogenic
26	Persistent elevated liver enzymes, congenital heart anomalies	NGS	Unknown	NM_000214.2(JAG1): C.1052delG; p.(Cys351 Leufs*61)	AD	Heterozgous	Pathogenic
27	Elevated liver enzymes and hepatosplenomegaly	NGS	WES	NM_000443.4(ABCB4):c.3634-4A>G; p.? NM_000443.4(ABCB4):c.1864G>T; p.(Gly622Trp)	AD/AR	Compound heterozygous	VUS
28	Elevated liver enzymes and hepatosplenomegaly	NGS	Custom gene panel	NM_000443.4(ABCB4):c.158A>T; p.(Asp53Val) NM_004004.6(GJB2):c.-23+1G>A; p.?NM_001042351.3(G6PD):c.563C>T; p.(Ser188Phe)	AR AR X-linked recessive	Homozygous homozygous hemizygous	VUS pathogenic pathogenic
34	Direct hyperbilirubinemia	Sanger	Targeted variant analysis	NM_025193.4(HSD3B7):c.45_46del; p.(Gly17 Leufs*26)	AR	Homozygous	Pathogenic
35	Persistent indirect hyperbilirubinemia	NGS	Gilbert syndrome genetic test	NM_000463.3(UGT1A1): C.-41_-40dupTA; p.?	AR	Homozygous	Pathogenic
37	Persistent indirect hyperbilirubinemia	NGS	Crigler-Najjar syndrome genetic test	NM_000463.3(UGT1A1): C.-41_-40dupTA; p.?	AR	Homozygous	Pathogenic
38	Persistent indirect hyperbilirubinemia	NGS	UGT1A1 full gene sequencing	NM_000463.3(UGT1A1): C.-41_-40dupTA; p.?	AR	Homozygous	Pathogenic
40	Direct hyperbilirubinemia	NGS	WGS	4.70 Mb deletion JAG1 gene 20p12	AD	Heterozygous	Pathogenic
43	Chronic pancreatitis	NGS	WES	NM_002769.4(PRSS1):c.365G>A; p.(Arg122His)	AD	Heterozygous	Pathogenic
44	Recurrent pancreatitis	NGS	Pancreatitis panel	NM_007272.3 (CTRC):c.738_761del; p.(Lys247_Arg254del)	AD	Heterozygous	Pathogenic
45	Chronic congenital diarrhea	NGS	Custom gene panel	NM_021102.4(SPINT2):c.442C>T; p.(Arg148Cys) NM_000277.3(PAH):c.157C>T; p.(Arg53Cys) NM_144687.4(NLRP12):c.1854C>G;p.(Tyr618*)	AR AR AD	Homozygous homozygous heterozygous	LP LP LP
48	Chronic congenital diarrhea	NGS	Unknown	NM_001080467.3(MYO5B):c.1966C>T; p.(Arg656Cys)	AR	Homozygous	LP
49	Chronic congenital diarrhea	NGS	Unknown	17 kb deletion in EPCAM gene 2p21	-	-	-
50	Chronic congenital diarrhea	NGS	Unknown	NM_001080467.3(MYO5B):c.1966C>T; p.(Arg656Cys)	AR	Homozygous	LP
51	Chronic congenital diarrhea, albinism, dysmorphism	NGS	Unknown	NM_014639.4(SKIC3):c.4070del; p.(Pro1357 Leufs*10)	AR	Homozygous	LP
52	Chronic congenital diarrhea	NGS	Chronic Congenital Diarrhea panel	NM_001080467.3(MYO5B):c.82del; p.(Thr28Profs*47)	AR	Homozygous	LP
53	FTT, persistent diarrhea, direct hyperbilirubinemia	NGS	Cholestasis panel	NM_020198.3(CCDC47):c.1234C>T; p.(Arg412*)	AR	Homozygous	LP
56	Non-mechanical intestinal obstruction, diarrhea	NGS	WES	NM_000111.2(SLC26A3):c.559G>T; p.(Gly187*)	AR	Homozygous	Pathogenic
57	FTT	NGS	Custom gene panel	NM_006408.4(AGR2):c.104del; p.(Asp35Alafs*38)	AR	Homozygous	LP
58	Chronic congenital diarrhea	NGS	WESTRIO	NM_001080467.2(MYO5B):c.2062C>T; p.(Arg688*) NM_000463.2(UGT1A1):c.1075G>A; p.(Asp359Asn) NM_000492.3(CFTR):c.1163C>T; p.(Thr388Met)	AR	Homozygous heterozygous heterozygous	Pathogenic VUS VUS
59	FTT, and chronic congenital diarrhea	NGS	WES	NM_012079.5(DGAT1):c.1374G>A; p.(Trp458*)	AR	Homozygous	LP
61	FTT	NGS	Cystic fibrosis panel	NM_000492.4(CFTR):c.1521_1523del; p.(Phe508del)	AR	Homozygous	Pathogenic
63	FTT	Sanger	Targeted variant analysis	NM_001012331.1(NTRK1):c.1624del; p.(Glu542Argfs*110)	AR	Homozygous	LP
64	FTT	NGS	Comprehensive lung panel	NM_001013838.3(CARMIL2):c.950dup; p.(Pro318Thrfs*44)	AR	Homozygous	LP
65	FTT	NGS	WESTRIO	NM_004333.6(BRAF):c.1574T>C; p.(Leu525Pro)	AD	Heterozygous	Pathogenic
68	Ileal mass and polyps	NGS	Unknown	NM_000455.5(STK11):c.300dup; p.(Gly622Trp)	AD	Heterozygous	LP
69	Multiple Polyp on multiple occasions	NGS	Unknown	STK11 gene deletion (unknown)	AD	Heterozygous	Pathogenic

IBD: Inflammatory bowel disease; NGS: Next-generation sequencing; CMA: Chromosomal microarray analysis; WES: Whole exome sequencing; FTT: Failure to thrive; AD: Autosomal dominant; AR: Autosomal recessive, LP: Likely pathogenic; VUS: Variant of uncertain significance; WESTRIO: Whole exome sequencing trio.