Cystic kidney disease
Gene: ALG9Comment 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, 3 p.m. | Last Modified: 20 Oct 2020, 3 p.m.
Panel Version: 2.19
Comment on mode of inheritance: Updated MOI to match review by Eleanor Williams.Created: 7 May 2020, 2:36 p.m. | Last Modified: 7 May 2020, 2:36 p.m.
Panel Version: 2.5
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 Gillessen-Kaesbach-Nishimura syndrome, 263210 (AR) in OMIM in which Polycystic kidneys is listed as a clinical feature.
PMID: 31395617 - Besse et al 2019 - report 2 patients in a clinically defined cohort with genetically unresolved polycystic liver and kidney disease that had rare heterozygous loss-of-function variants in ALG9. Then using a novel ‘genotype-first’ approach to find ALG9 mutation carriers from a large cohort of exome-sequenced individuals, they found that 7/8 (88%) of ALG9 mutation carriers over age 50 had a least 4 kidney cysts (abstract only accessed).
PMID: 28932688 - Davis et al 2017 - report the case of a proband with ALG9-CDG who has a milder phenotype. This female child was born to non-consanguineous parents of Scottish decent. Prenatally, dysmorphic features, numerous renal cysts and minor cardiac malformations were detected. Post-natally, dysmorphic features included shallow orbits, micrognathia, hypoplastic nipples, talipes equinovarus, lipodystrophy and cutis marmorata. She developed failure to thrive and seizures. A homozygous mutation in ALG9, c.860A > G (p.Tyr287Cys) was identified. Both parents were found to carry one copy of the mutation. In a table of phenotypic features from the 11 known patients with ALG9-CDG (including the one here), 3 other patients are reported with polycystic kidneys and homozygous ALG variants.Created: 12 Nov 2019, 4:49 p.m. | Last Modified: 12 Nov 2019, 4:50 p.m.
Panel Version: 2.0
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Gillessen-Kaesbach-Nishimura syndrome, 263210
Publications
Sources: Expert ReviewCreated: 25 Oct 2019, 8:32 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
cystic liver disease; cystic kidney disease
Publications
Tag for-review was removed from gene: ALG9.
Source Expert Review Green was added to ALG9. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: alg9 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: ALG9.
Gene: alg9 has been classified as Green List (High Evidence).
Phenotypes for gene: ALG9 were changed from cystic liver disease; cystic kidney disease to cystic liver disease; cystic kidney disease; Gillessen-Kaesbach-Nishimura syndrome, 263210
Publications for gene: ALG9 were set to 31395617
Mode of inheritance for gene: ALG9 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
gene: ALG9 was added gene: ALG9 was added to Cystic kidney disease. Sources: Expert Review Mode of inheritance for gene: ALG9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALG9 were set to 31395617 Phenotypes for gene: ALG9 were set to cystic liver disease; cystic kidney disease Penetrance for gene: ALG9 were set to Complete Review for gene: ALG9 was set to GREEN