Copyright
©The Author(s) 2020.
World J Gastroenterol. Feb 7, 2020; 26(5): 550-561
Published online Feb 7, 2020. doi: 10.3748/wjg.v26.i5.550
Published online Feb 7, 2020. doi: 10.3748/wjg.v26.i5.550
TJP2 status | P1.1 | P1.2 | P2.1 | P2.2 | P2.3 | P2.4 | P2.5 | P2.6 | P2.7 | P2.8 | P2.9 | P2.10-12 |
+/wt | +/wt | +/+ | +/wt | wt/wt | +/+ | +/+ | +/+ | +/+ | +/wt | +/+ | NA | |
Gender | M | F | M | F | M | M | M | F | M | M | M | F, F, F |
Age in 2018 (yr) | 60 | 55 | 36 | 32 | 31 | 25 | 23 | 21 | 19 | 16 | 15 | NA |
ALAT (< 45 female; < 70 male; (U/L) | 16 | 19 | 114 | 15 | 10 | 43 | 37 | 44 | 97 | 21 | 22 | NA |
Bilirubin (5-25 μmol/L) | 8 | 4.7 | 29 | 4.4 | 14 | 12 | 45 | 10 | 17 | 14 | 11 | NA |
Alkaline phosphatase (35-105 U/L) | 101 | 104 | 120 | 65 | 50 | 112 | 212 | 117 | 115 | 104 | 121 | NA |
GGT (10-80 U/L) | 72 | 21 | 61 | 14 | 12 | 44 | 156 | 55 | 86 | 12 | 15 | NA |
Coagulation II, VII, X/INR | 1.0 | 1.2 | 1.2 | 0.81 | 1 | 1.2 | 1.7 | 1.1 | 0.73 | 0.75 | 0.72 | NA |
Albumin (36-48 g/L) | 44 | 41 | 36 | 37 | 44 | 46 | 29 | 37 | 27 | 44 | 47 | NA |
Creatinine (60-105 μmol/L) | 68 | 40 | 71 | 49 | 62 | 68 | 66 | 37 | 71 | 67 | 53 | NA |
Cholesterol (< 5.0 mmol/L) | 5.7 | 6.5 | 5 | 4.3 | 3.4 | 3.8 | 3.2 | 4.4 | NA | 3.3 | 4.7 | NA |
HDL cholesterol (> 1.0 mmol/L) | 0.91 | 1.1 | 1.8 | 2.0 | 0.92 | 2 | 1.7 | 1.9 | NA | 1.1 | 1.3 | NA |
LDL cholesterol (< 3 mmol/L) | 3.3 | 3.7 | 2.7 | 1.9 | 2.2 | 1.4 | 1.1 | 2.2 | NA | 1.8 | 3 | NA |
Triglyceride (< 2 mmol/L) | 3.3 | 3.5 | 1.1 | 0.9 | 1.1 | 1 | 1 | 0.7 | NA | 0.9 | 1 | NA |
Leucocytes (3.5-10.0 10^9/L) | 11.7 | 4.72 | 4.19 | 6.96 | 5.8 | 7.03 | 4.25 | 6.44 | 5.78 | 7.8 | 5.7 | NA |
Hemoglobin (> 7.3 female; > 8.3 male, mmol/L) | 9.4 | 7.8 | 9.3 | 7.5 | 9.9 | 10.1 | 7.8 | 8 | 9.9 | 10.3 | 9.6 | NA |
Platelets (165-400, × 109/L) | 335 | 405 | 77 | 266 | 229 | 218 | 64 | 191 | 210 | 379 | 339 | NA |
sCD163 (0.69-3.86 mg/L) | 2.32 | 1.94 | NA | 1.90 | 2.95 | 3.96 | 5.23 | 6.03 | 3.91 | 1.31 | 1.75 | NA |
FibroScan (kPa) | 4.4 | 3.3 | 75 | 4-7 | 6.6 | 8.1 | 24 | 9.1 | 5.9 | 5.7 | 7.8 | NA |
Patient ID | Age (yr) | Gender | TJP2 variation | TJP2 genotype | Other gene variations | Phenotype |
P2.1 | 36 | M | TJP2 [NM_004817.3]:c.[3334C>T];[3334C>T] | Homozygous | ABCB11[NM_003742.2]:c.[1331T>C];[=] | PFIC4 with cirrhosis, portal hypertension and acute-on-chronic liver failure; Liver transplantation |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
UGT1A1[NM_000463.2]C.-53TA[6];[7] | ||||||
P2.5 | 23 | M | TJP2 [NM_004817.3]:c.[3334C>T];[3334C>T] | Homozygous | ABCB11[NM_003742.2]:c.[1331T>C];[1331T>C]2 | PFIC4 with cirrhosis, portal hypertension. Primary liver cancer; Liver transplantation |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
P2.4 | 25 | M | TJP2 [NM_004817.3]:c.[3334C>T];[3334C>T] | Homozygous | ABCB11[NM_003742.2]:c.[1331T>C];[1331T>C]2 | Elevated liver enzymes |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
P2.6 | 21 | F | TJP2 [NM_004817.3]:c.[3334C>T];[3334C>T] | Homozygous | ABCB11[NM_003742.2]:c.[1331T>C];[=] | Elevated liver enzymes; Severe cholestasis in pregnancy |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
UGT1A1[NM_000463.2]C.-53TA[6];[7] | ||||||
P2.7 | 19 | M | TJP2 [NM_004817.3]:c.[3334C>T];[3334C>T] | Homozyg-ous | ABCB11[NM_003742.2]:c.[1331T>C];[=] | Elevated liver enzymes |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
UGT1A1[NM_000463.2]C.-53TA[6];[7] | ||||||
P1.1 | 60 | M | TJP2 [NM_004817.3]:c.[3334C>T];[3334=] | Heterozyg-ous | ABCB11[NM_003742.2]:c.[1331T>C];[1331T=] | Normal |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
UGT1A1[NM_000643.2]C.-53TA[6];[7] | ||||||
P1.2 | 55 | F | TJP2 [NM_004817.3]:c.[3334C>T];[3334=] | Heterozyg-ous | ABCB11[NM_003742.2]:c.[1331T>C];[=] | Normal |
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
P2.2 | 32 | F | TJP2 [NM_004817.3]:c.[3334C>T];[3334=] | Heterozygous | ABCB11[NM_003742.2]:c.[1331T>C];[=] | Mild cholestasis in pregnancy |
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
P2.8 | 16 | M | TJP2 [NM_004817.3]:c.[3334C>T];[=] | Heterozygous | ABCB11[NM_003742.2]:c.[1331T>C];[1331T=]1 | Normal |
ABCG5[NM_022436.2]:c.[148C>T];[=] | ||||||
UGT1A1[NM_000463.2]C.-53TA[6];[7] | ||||||
P2.3 | 31 | M | TJP2 [NM_004817.3]:c.[3334=];[3334=] | Wild type | ABCG5[NM_022436.2]:c.[148C>T];[=] | Normal |
P2.9 | 15 | M | TJP2 [NM_004817.3]:c.[3334=];[3334=] | Wild type | ABCB11[NM_003742.2]:c.[1331T>C];[1331T>C]2 | Normal |
ABCC2[NM_000392.3]:c.[3563T>A];[4544G>A]1 | ||||||
P2.10 | - | F | - | - | Mild cholestasis, 4 pregnancies? | |
P2.11 | - | F | - | - | Mild cholestasis, 3 pregnancies? | |
P2.12 | - | F | - | - | Mild cholestasis, 2 pregnancies? |
Ref. | TJP2 gene | Age | Liver enzymes | Bile acids | Fibrosis | Pruritus | ICP | HCC | Liver failure | TJP2 mutation | TJP2/Included |
Vitale et al[2] | Heterozyg-ous | 37-51 yr | Elevated | Elevated | Normal FibroScan | 1 with obvious symptoms | 1 with DIC and ICP | NK | NK | p.[T62M]; [=]p.[I875T]; [=] | 10/48 |
Sambrotta et al[6] | 12 children Homozyg-ous | 1-3 mo | Low or normal | Elevated | Cirrhosis and portal hypertension age 4 and 7 | No | No | Not described | 9 liver transplantations | c.766_769delGCCT, c.885delC | 12/12 |
1.5-4 years age | c.782delA, c.1361delC, c.1992-2A>G, c.953-735_2356-249del | ||||||||||
1 died 13 months | c.3408-?_3573+?del and c.1894C>T | ||||||||||
Wang et al[10] | 21-68 yr | NK | NK | NK | NK | NK | NK | NK | c.2081G>A(p.G694E) | 8/21 Hearing loss | |
Dixon et al[11] | Heterozyg-ous | NK | Elevated | Elevated | NK | Yes | All confirmed ICP | NK | NK | p.Thr62Met; p.Thr626Ser | 3/26 |
1 stillbirth | c.1877C > G. p.Thr626Aer | ||||||||||
Ge et al[14] | Compound heterozyg-ous | 23 mo | Elevated | Elevated | NK | Alleviated after treatment | - | NK | NK | c.2448 + 1G > C | 1/1 |
c.2639delC (p.T880Sfs*12) | |||||||||||
Zhou et al[15] | Compound heterozyg-ous | 26 mo | Elevated | NK | Both with cirrhosis | NK | No | Yes | Yes | 2668-1G>T /c.2438dupT (p.Asn814Glnfs | 2/2 |
Homozyg-ous | 6 mo | Elevated | Yes, age 2 years | NK | c.817delG (p.A273fs | ||||||
Vij et al[16] | Homozyg-ous | 7 yr | Normal | Elevated | Cirrhotic explant liver and high-grade dysplastic nodule | Yes | No | Yes, early well- differentiated | No | c.(2659+1_2660-1)/(2760+1_2761-1) | 1/1 |
Shagrani et al[17] | Heterozyg-ous | 0-12 yr | Elevated | Normal | 1 with congenital hepatic fibrosis | No | No | No | NK | c.2038delA:p.R680fs | 12/37 |
Homozyg-ous | But 4 patients required liver transplantation | c.1012C>T:p.R338X | |||||||||
c.1012C>T:p.R338X | |||||||||||
c.1013delG:p.R338fs | |||||||||||
c.1190C>T:p.P397L | |||||||||||
c.1373delC:p.A458fs | |||||||||||
c.1373delC:p.A458fs | |||||||||||
Chen et al[18] | Heterozyg-ous | > 1 yr | NK | Elevated but no detailed data | NK | No | No | No | NK | c.2174G>A, | 4/33 |
c.343A>G/c.1377T>G | |||||||||||
c.343A>G/c.1377T>G | |||||||||||
c.925C>T | |||||||||||
Carlton et al[19] | Homozyg-ous | 1-8 yr | Almost normal | Almost normal or NK | NK | Yes | NK | NK | NK | 143C/143C | 11 individuals with familial hypercholanemia in 8 families |
Mutated gene (deficiency) | Disease association (autosomal recessive) | Disease association (autosomal dominant) |
ATP8B1(FIC1) | PFIC1(2009) BRIC1 | ICP |
ABCB11(BSEP) | PFIC2(2009) BRIC2 | ICP Drug-induced cholestasis |
ABCB4 (MDR3) | PFIC3 | ICP LPAC Drug-induced cholestasis |
TJP2(TJP2) | PFIC4 | ICP |
ABCC2(MRP2) | Dubin-Johnson | ICP |
ABCG5(ABCG5) | Sitosterolemia | Cholelithiasis |
UGT1A1(UGT1A1) | Crigler-Najjar syndrome type 1; Crigler-Najjar syndrome type 2; Gilbert syndrome (promotor regions) | |
NR1H4(FXR) | Intralobular cholestasis | Posttransplant hepatic steatosis |
MYO5B(MYO5B) | Microvillus inclusion disease (MVID); Cholestasis without MVID |
- Citation: Wei CS, Becher N, Blechingberg J, Ott P, Vogel I, Grønbæk H. New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report. World J Gastroenterol 2020; 26(5): 550-561
- URL: https://www.wjgnet.com/1007-9327/full/v26/i5/550.htm
- DOI: https://dx.doi.org/10.3748/wjg.v26.i5.550