Relationship of familial cytochrome P450 4V2 gene mutation with liver cirrhosis: A case report and review of the literature

Table 1 Changes of liver function indicators in the index patient

Date	ALT, U/L	AST, U/L	TBIL, μmol/L	DBIL, μmol/L	IBIL μmol/L	GGT, U/L	ALP, U/L	ALB, g/L	GLO, g/L
	Ref: 0-40	Ref: 0-34	Ref: 5.1-19.0	Ref: 1.7-6.8	Ref: 1.7-13.2	Ref: 0-50	Ref: 40-150	Ref: 38-51	Ref: 20-30
2020-10-14	89.9↑	259.6↑	94.13↑	44.45↑	49.68↑	40.70	178.7↑	25.30↓	51.7↑
2020-10-20	58.9↑	164.7↑	90.92↑	39.89↑	51.03↑	35.77	158.5↑	33.03↓	43.0↑
2021-01-14	86.9↑	182.5↑	109.91↑	60.62↑	49.28↑	37.60	69.9	21.20↓	55.3↑
2021-01-26	61.0↑	159.2↑	71.90↑	44.26↑	27.64↑	28.60	87.5	27.70↓	30.0
2021-04-18	63.7↑	204.4↑	102.32↑	68.26↑	34.06↑	31.40	117.4	24.00↓	35.6↑
2021-04-25	46.2↑	151.8↑	79.40↑	53.25↑	26.15↑	28.80	105.3	30.60↓	32.3↑
2021-07-14	53.3↑	164.7↑	95.24↑	65.73↑	29.51↑	34.00	116.7	25.30↓	34.7↑
2021-07-25	36.72	113.5↑	80.00↑	57.63↑	22.37↑	-	-	33.78↓	27.7

Here and below: Bold number with upward arrow, abnormally high; bold number with downward arrow, abnormally low. ALT: Alanine transaminase; AST: Aspartate aminotransferase; TBIL: Total bilirubin; DBIL: Direct bilirubin; IBIL: Indirect bilirubin; GGT: Gamma glutamyl transpeptidase; ALP: Alkaline phosphatase; ALB: Albumin; GLO: Globulin.

Table 2 Changes of blood cell counts and hemoglobin in the index patient

Date	WBCs, × 109/L	RBCs, × 1012/L	HB, g/L	PLTs, × 109/L
	Ref: 3.5-9.5	Ref: 3.8-5.1	Ref: 115-150	Ref: 125-350
2020-10-14	3.25↓	3.5↓	120	62↓
2021-01-13	8.94	3.3↓	122	46↓
2021-01-26	2.56↓	2.8↓	97↓	50↓
2021-04-18	3.21↓	2.9↓	102↓	58↓
2021-04-22	2.49↓	2.7↓	108↓	51↓
2021-07-14	3.13↓	3.0↓	105↓	56↓

HB: Hemoglobin; PLTs: Platelets; RBCs: Red blood cells; WBCs: White blood cells.

Table 3 Changes of coagulation function indicators in the index patient

Date	INR	PT, s	APTT, s	FIB, g/L
	Ref: 0.8-1.3	Ref: 10.0-15.0	Ref: 21.0-35.0	Ref: 2.0-4.0
2020-10-14	1.53↑	17.03↑	56.73↑	1.54↓
2021-01-13	1.25	15.60↑	31.63	2.06
2021-01-26	1.47↑	17.90↑	38.77↑	1.24↓
2021-04-18	1.54↑	18.79↑	42.95↑	1.30↓
2021-04-22	1.58↑	19.36↑	43.93↑	1.18↓
2021-07-15	1.43↑	17.02↑	39.93↑	1.37↓

APTT: Activated partial thromboplastin time; FIB: Fibrinogen; INR: International normalized ratio; PT: Prothrombin time.

Table 4 Changes of thyroid function indicators in the index patient

Date	T3, ng/mL	T4, µg/dL	FT3, pg/mL	FT4, ng/dL	TSH, µIU/mL
	Ref: 1.3-3.1	Ref: 5.0-14.5	Ref: 2.3-4.0	Ref: 0.6-1.2	Ref: 0.35-5.10
2020-10-14	0.66↓	9.27	2.14↓	0.94	5.18↑
2021-01-13	0.62↓	7.65	2.17↓	0.96	4.74
2021-07-26	0.43↓	5.62	1.57↓	0.91	6.56↑

FT3: Free triiodothyronine; FT4: Free thyroxine; T3: Triiodothyronine; T4: Thyroxine; TSH: Thyroid stimulating hormone.

Table 5 Serological test results of the index patient (II-1) and her relatives

Patient	ALT, U/L	AST, U/L	TBIL, μmol/L	HDL-C, mmol/L	APOA1, g/L	T3, ng/mL	TSH, µIU/mL
	Ref:0-40	Ref: 0-34	Ref: 5.1-19.0	Ref: 1.29-1.55	Ref: 1.0-1.6	Ref: 1.3-3.1	Ref: 0.35-5.1
I-1	23	41↑	10.1	1.51	1.57	1.74	2.99
II-1	53.3↑	164.7↑	95.2↑	1.42	1.50	0.43↓	6.56↑
II-2	19	54↑	18.2	1.88↑	1.79↑	1.96	6.54↑
II-3	26	59↑	13.2	1.42	1.52	1.83	1.70
II-4	20	50↑	29.8↑	1.17↓	ND	1.50	5.29↑
II-5	10	28	22.8↑	1.94↑	1.83↑	1.29↓	1.55
II-6	22	41↑	16.4	1.52	1.71↑	2.14	3.13

ALT: Alanine transaminase; APOA1: Apolipoprotein A-I; AST: Aspartate aminotransferase; HDL-C: High density lipoprotein cholesterol; T3: Triiodothyronine; TBIL: Total Bilirubin; TSH: Thyroid stimulating hormone.

Table 6 Total exome sequencing results of gene mutations in the index patient (II-1) and her relatives

Patient	Gene	Chromosome location	Basic variation	Zygosity	Inheritance pattern
I-1	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HTZ	AR
I-2	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HTZ	AR
II-1	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HMZ	AR
	DUOXA2	chr15: 45408785	c.413dupA	HTZ	AR
II-2	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HTZ	AR
II-3	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HMZ	AR
	DUOXA2	chr15: 45408785	c.413dupA	HTZ	AR
II-5	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HTZ	AR
	DUOXA2	chr15: 45408785	c.413dupA	HTZ	AR
II-6	CYP4V2	chr4: 187122319	c.802-8_810delinsGC	HMZ	AR

AR: Autosomal recessive; CYP4V2: Cytochrome P450 4V2; DUOXA2: Dual oxidase activator 2; HMZ: Homozygous; HTZ: Heterozygous.