Human Mutation

Research Article

Splicing Analysis of MYO5B Noncanonical Variants in Patients with Low Gamma-Glutamyltransferase Cholestasis

Table 1

Clinical findings and identified MYO5B variants in new low GGT cholestasis patients.


	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5

Variants	c.335C>G/p.(Pro112Arg) c.1669-35A>C	c.455+8T>C	c.4637C>T/p.(Thr1546Met) c.2415-6C>G	c.613-11G>A c.2996_2998del/p.(Arg999_Lys1000delinsGln)	c.4221G>A/p.(=) c.1669-2_1669-1delinsTT
Zygosity	Compound heterozygote	Homozygote	Compound heterozygote	Compound heterozygote	Compound heterozygote
Sex/age at presentation	Male/1 m	Male/2 m	Male/1 m 10 d	Male/1y 7 m	Male/3 m
Liver manifestations	Jaundice, pruritus	Jaundice, pruritus, hepatomegaly	Jaundice, pruritus, hepatomegaly, splenomegaly, liver failure	Jaundice, pruritus, hepatomegaly	Jaundice, pruritus, hepatomegaly
Liver biopsy age/findings	2 y 1 m/canalicular cholestasis, mild portal inflammation	1 y 1 m/canalicular cholestasis, mild portal inflammation, slight ductular reaction	ND	1 y 8 m/hepatocellular and canalicular cholestasis, ballooning degeneration of hepatocytes, portal fibrosis and mild inflammation, ductular reaction, and reduction of interlobular ductules	1 y 4 m/mild portal fibrosis and inflammation and features suggestive of chronic cholestasis
Extrahepatic abnormalities	None	None	Right hydrocele, atrial septal defect, and patent foramen ovale	Enlargement of the kidney and α1-microglobinuria	Hypothyroidism, severe malnutrition, premature, and diarrhea
Management	UDCA, rifampicin, cholestyramine, phenobarbitone, fat-soluble vitamins	UDCA, rifampicin, cholestyramine, phenobarbitone, fat-soluble vitamins	UDCA, fat-soluble vitamins	UDCA, rifampicin, cholestyramine, fat-soluble vitamins	UDCA, cholestyramine, phenobarbitone, fat-soluble vitamins, Euthyrox
Status at first assessment
Age	4 m	4 m	2 m 23 d	1 y 7 m	3 m
Pruritus	–	–	–	+	–
Hepatomegaly	–	+	+	+	–
Splenomegaly	–	–	+	–	–
TB (3.4-17.1 μmol/L)	112.6	264	274.8	227.7	30
DB (0-6 μmol/L)	79.2	231.4	196.2	157.8	26
ALT (9-50 IU/L)	517	40.3	299	156	479
AST (15-40 IU/L)	572	61.7	196	114	187
GGT (8-57 IU/L)	46	27.9	54	13	47
TBA (0-10 μmol/L)	101.8	141.5	165.7	436.7	109
ALB (40-55 g/L)	43.6	40.5	41.8	43.4	44
PT (11-14.5 s)^†	ND	12.3	43	ND	ND
Status at most recent assessment
Age	2 y 4 m	2 y 5 m	2 y 5 m	3 y 4 m	2 y
Pruritus	+	+	–	+	+
Hepatomegaly	–	+	–	+	–
Splenomegaly	–	–	–	–	–
TB (3.4-17.1 μmol/L)	94.8	114.1	5	104.1	215.3
DB (0-6 μmol/L)	84.6	88.6	2.1	77	163.8
ALT (9-50 IU/L)	37	35.3	25.37	39.88	171.12
AST (15-40 IU/L)	68	65.2	43.53	59.73	125.57
GGT (8-57 IU/L)	8	18	7.8	7.95	11.32
TBA (0-10 μmol/L)	290.2	185.5	3.9	103	380.80
ALB (40-55 g/L)	44.5	37.5	43.4	39.37	34.74
PT (11-14.5 s)^†	12.0	12.2	13.8	11	12.2
Weight centile	3^rd-10^th	<3^rd	75^th	25^th-50^th	<3^rd
Height centile	<3^rd	<3^rd	90^th	25^th-50^th	<3^rd
Outcome	Mild jaundice, pruritus, poor growth	Mild jaundice, pruritus, poor growth	Atrial septal defect	Jaundice and pruritus	Jaundice, pruritus, poor growth

Normal ranges are given in parentheses. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DB, directed bilirubin; d, day(s); GGT, gamma-glutamyltransferase; m, month(s); NA, not available; ND, not done; PT, prothrombin time; s, seconds; TB, total bilirubin; TBA, total bile acids; y, year(s); +, present; –, absent. ^†Values after supplementation of vitamin K.