Fetal anomalies
Gene: ALG9The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.
Panel Version: 1.836
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel. Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene.
Green on related panel(s): Congenital disorders of glycosylation; Cystic renal disease (super panel); Skeletal dysplasia
See previous reviews for detailsCreated: 29 Jan 2021, 12:40 p.m. | Last Modified: 29 Jan 2021, 12:40 p.m.
Panel Version: 1.229
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital disorder of glycosylation, type Il, 608776
Comment on list classification: Change from Green to Amber as requested by NHSE for sign-off panelCreated: 19 Aug 2020, 6:13 p.m. | Last Modified: 19 Aug 2020, 6:13 p.m.
Panel Version: 1.81
CDGs can present prenatally with hydrops fetalis; please note three patients with ALG9 variants reported in recent literature review of CDGs/hydrops.Created: 30 Dec 2019, 10:33 a.m. | Last Modified: 30 Dec 2019, 10:33 a.m.
Panel Version: 1.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital disorder of glycosylation, type Il, MIM#608776
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: ALG9 congenital disorder of glycosylation has a broad phenotype and can include non-immune hydrops/NIHF (PMID:26453364 and 31420886). Although the NIHF phenotype is not consistent, even within families carrying the same variant, there are additional prenatal phenotypes reported in the literature for ALG9 cases: 3 fetally-lethal cases of skeletal dysplasia in PMID:25966638, and an individual with multiple malformations detected prenatally in PMID:28932688. Overall: fetally-relevant phenotype and sufficient cases for inclusion on panel and have therefore increased rating from Amber to Green.Created: 7 May 2020, 2:15 p.m. | Last Modified: 7 May 2020, 2:15 p.m.
Panel Version: 1.52
PMID:28932688. Davis et al., 2017 review the literature for ALG9:CDG cases. They summarise 10 patients from 6 different families with one of four ALG9 variants. In addition to summarising the 3 patients from Tham et al (PMID:25966638) who died in utero, they report an additional patient with ALG9-CDH with a milder phenotype. Prenatally, dysmorphic features, renal cysts and cardiac malformations were detected. She had a homozygous variant in ALG9: p.Tyr287Cys.Created: 7 May 2020, 2:06 p.m. | Last Modified: 7 May 2020, 2:06 p.m.
Panel Version: 1.49
PMID:25966638 (Tham et al) performed fetal autopsy on 3 affected fetuses who died in utero from 2 unrelated families (from Turkey and Iraq) with Gillessen-Kaesbach-Nishimura syndrome (AR lethal skeletal dysplasia). All patients were homozygous for a splicing variant in ALG9 (NM_024740.2: c.1173+2T>A).Created: 7 May 2020, 2:05 p.m. | Last Modified: 7 May 2020, 2:05 p.m.
Panel Version: 1.49
PMID:31420886 Makhamreh et al., 2020 provide a literature review of Nonimmune hydrops fetalis (NIHF) and congenital disorders of glycosylation. 3/15 families had NIHF and ALG9 variants (20%). Full text unavailable at time of curation.Created: 7 May 2020, 1:38 p.m. | Last Modified: 7 May 2020, 1:38 p.m.
Panel Version: 1.46
PMID:26453364. AlSubhi et al., 2016 summarise 6 patients with ALG9-CDG from the literature and report 4 additional patients from a large consanguineous family. Patient IV:3/patient4 (a male cousin of the index patient) presented with nonimmune hydrops fetalis diagnosed by fetal US at 28 weeks, and a novel homozygous variant p.E350K in the ALG9 gene. Table 2 doesn't list Hydrops in any of the previous patients.Created: 7 May 2020, 1:31 p.m. | Last Modified: 7 May 2020, 1:31 p.m.
Panel Version: 1.46
DDG2P rating in original PAGE list: Probable for ALG9-CDGCreated: 11 Dec 2018, 9:04 a.m.
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)
Tag for-review tag was added to gene: ALG9.
Gene: alg9 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ALG9 were changed from AR lethal skeletal dysplasia; ALG9-CDG; Congenital disorder of glycosylation, type Il, 608776; NIHF; hydops fetalis to Gillessen-Kaesbach-Nishimura syndrome, 263210; AR lethal skeletal dysplasia; ALG9-CDG; Congenital disorder of glycosylation, type Il, 608776; NIHF; hydops fetalis
Gene: alg9 has been classified as Green List (High Evidence).
Tag for-review was removed from gene: ALG9.
Phenotypes for gene: ALG9 were changed from ALG9-CDG; Congenital disorder of glycosylation, type Il, 608776; NIHF; hydops fetalis to AR lethal skeletal dysplasia; ALG9-CDG; Congenital disorder of glycosylation, type Il, 608776; NIHF; hydops fetalis
Publications for gene: ALG9 were set to 26453364; 31420886
Tag for-review tag was added to gene: ALG9.
Gene: alg9 has been classified as Amber List (Moderate Evidence).
Publications for gene: ALG9 were set to
Phenotypes for gene: ALG9 were changed from ALG9-CDG to ALG9-CDG; Congenital disorder of glycosylation, type Il, 608776; NIHF; hydops fetalis
gene: ALG9 was added gene: ALG9 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: ALG9 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ALG9 were set to ALG9-CDG