Cystic kidney disease

Gene: ALG8

In Schollen et al 2004 (PMID: 15235028) reports biallelic ALG8 variants in congenital disorders of glycosylation type Ih. One of the cases reported has multiple cystic dilated intra- and extrahepatic bile ducts, cholestasis, bilateral microcysts in all parts of the kidney in one case with c.672+4A.G in intron 6 and the missense mutation p.G275D (c.824G>A). Although this case is relevant to this panel, it does not justify biallelic mode of inheritance being applied to ALG8 variants in this panel.

Created: 29 Mar 2022, 2:07 p.m. | Last Modified: 29 Mar 2022, 2:07 p.m.

Panel Version: 2.36

Publications

• 15235028

Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).

Created: 20 Oct 2020, 2:59 p.m. | Last Modified: 20 Oct 2020, 2:59 p.m.

Panel Version: 2.18

Green List (high evidence)

The rating and mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 7 Mar 2022, 3:39 p.m. | Last Modified: 7 Mar 2022, 3:39 p.m.

Panel Version: 2.33

Associated with Polycystic liver disease 3 with or without kidney cysts, 617874 (AD) in OMIM.

PMID: 28375157 - Besse et al 2017 - report 5 probands with 3 different heterozygous variants in ALG8 and liver cysts. 4 of the probands also had between 1 and 9 kidney cysts (1, at least 3, 3-4 and 9). 3 of the probands share the same c.1090C>T, p.R364X variant, but the shared haplotype block among any 2 of these individuals is approximately 87 kb which is too small to be indicative of a cryptic relationship between any of the probands and instead suggests that the mutation in each arose independently. The proband with 3-4 kidney cysts has a daughter who shares the ALG8 variants and who has no liver cysts but 8 kidney cysts.

PMID: 30135240 - Lanktree et al 2018 - looked for rare variants in gnomAD and BRAVO in genes involved in ADPKD (PKD1, PKD2), ADPLD (PRKCSH, SEC63, GANAB, ALG8, SEC61B, LRP5). ADPLD protein truncating variants in ALG8 are found in 1 in 1,429 people in these two databases. But this paper does not give numbers of people with ADPLD or if those people also have kidney cysts.

Created: 12 Nov 2019, 2:37 p.m. | Last Modified: 13 Nov 2019, 12:49 p.m.

Panel Version: 2.0

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Polycystic liver disease 3 with or without kidney cysts, 617874

Publications

• 28375157

Green List (high evidence)

Sources: Expert Review

Created: 25 Oct 2019, 8:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
cystic liver disease; cystic kidney disease

Publications

• 30135240