Table 1 Genetic and diagnostic determinants of PCLD and ADPKD

Genotype

Cytogenetic gene location (mutation frequency%)

Chr.19p13.2: PRKCSH (15%)

Chr.16p13.3: PKD1 (75.7%)

[62, 63]

Chr.6q21: SEC63 (5.7%)

Chr.4q21: PKD2 (13.4%)

Mutation (type; N,%)

25 PRKCSH 22 SEC63

980 PKD1 193 PKD2

[HGMD]

missense

4 (16%) 6 (27.3%)

250 (25%) 29 (15%)

splice site

4 (16%) 3 (13.6%)

77 (7.8%) 32 (16.6%)

insertion/deletion

10 (40%) 7 (31.8%)

440 (45%) 80 (41.5%)

indel

1 (4%) -

13 (1.4%) 7 (3.6%)

nonsense

6 (24%) 6 (27.3%)

202 (20%) 45 (23.3%)

complex rearrangement

-

8 (0.8%) -

Gene product; protein localization

Cholangiopathy

Ciliopathy

[13, 60]

Hepatocystin/ glucosidase II-β subunit; ER

Polycystin-1 (TRPP1); primary cilium, tight junction, extracellular matrix, ER

Translocation protein SEC63 homolog;

Polycystin-2 (TRPP2); primary cilium, tight junction, extracellular matrix, ER

ER, membrane complex

Protein function

Proper protein folding and protein quality control

PC-1 and PC-2 form a mechanosensor complex on the primary cilium

[13, 60]

Posttranslational protein transport

PC-1 for signaling detection, PC-2 is a TRP channel for calcium influx

Predominant phenotype

Liver features

Positive family history with:

Most common extra-renal manifestation: 83% with a polycystic liver (>20 hepatic cysts)

[14, 64]

PCLD diagnostic criteria:

Clinical practice:

<40 years and ≥1 hepatic cyst

≥40 years and ≥4 hepatic cysts

30-70 years and polycystic liver (>20 hepatic cysts)

Kidney features

Incidental finding without renal disease: 28-35% with renal cystogenesis

Positive family history with unknown genotype:

[15, 19, 65, 66]

ADPKD diagnostic criteria:

15-39 years and 3 renal cysts^#

40-59 years and 2 renal cysts*

≥60 years and 4 renal cysts*

Negative family history:

<30 years and 5 renal cysts^$

30-60 years and 5 renal cysts^$

>60 years and 8 renal cysts^$