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Fetal anomalies v2.0 UROS Gene migrated from ENSG00000188690 to ENSG00000188690 (gene set migration)
Fetal anomalies v1.588 CLUAP1 Sarah Milton changed review comment from: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature; to: CLUAP1 encodes Clusterin-associated protein 1 which localizes to the base and tip of cilia and associates with the intraflagellar transport (IFT) complex B group of proteins.

Leber congenital amaurosis (LCA)
PMID: 26820066 and 34209753 report biallelic variants in CLUAP1 in 2 individuals with Leber congenital amaurosis including severe visual dysfunction from birth and nystagmus.
Missense and splice variants were reported with functional studies to support a deleterious nature (Cell models/Zebrafish transfection and minigene splice assays). Other causative LCA genes are known to be involved in intraflagellar transport.
Biallelic zebrafish and mouse result in lethality in utero, zebrafish embryos at 5 days post fertilisation demonstrate lack of photoreceptor cells.
Amber for this association.

Ciliopathy
PMID 28679688 reports one individual with biallelic variants in CLUAP1 with a syndromic phenotype reminiscent of Joubert/orofaciodigital syndrome including dysmorphic features, rhizomelic limb shortening, polydactyly, molar tooth sign, midline teeth, oculomotor apraxia. One missense and one nonsense variant were noted with functional studies to support the deleterious nature.
Red for this association.

It is plausible the LCA and ciliopathy phenotypes are a spectrum of disease however there is insufficient evidence to indicate this currently.
Sources: Literature
Fetal anomalies v1.588 CLUAP1 Sarah Milton gene: CLUAP1 was added
gene: CLUAP1 was added to Fetal anomalies. Sources: Expert Review Red,Literature,Literature
Mode of inheritance for gene: CLUAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLUAP1 were set to 34209753; 28679688; 26820066
Phenotypes for gene: CLUAP1 were set to Leber congenital amaurosis, MONDO:0018998, CLUAP1-related; Ciliopathy, MONDO:0005308, CLUAP1-related
Fetal anomalies v0.3034 UROS Zornitza Stark Marked gene: UROS as ready
Fetal anomalies v0.3034 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Fetal anomalies v0.3034 UROS Zornitza Stark Classified gene: UROS as Green List (high evidence)
Fetal anomalies v0.3034 UROS Zornitza Stark Gene: uros has been classified as Green List (High Evidence).
Fetal anomalies v0.2892 UROS Krithika Murali gene: UROS was added
gene: UROS was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROS were set to 34187847; 34828434; 15065102
Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic - MIM#263700; hydrops fetalis; multiple congenital anomalies
Review for gene: UROS was set to GREEN
Added comment: Biallelic variants associated with congenital erytropoietic porphyria (CEP).

PMID 34187847 Khalouaoui A et al 2021 report one infant with CEP secondary to homozygous UROS variants. Prenatal ultrasound at 25 weeks of gestation revealed an increased nuchal translucency and myocardial hypertrophy.

PMID: 34828434 Arnaud et al 2021 - report one fetus miscarried in the 2nd trimester with 22 weeks ultrasound showing hyperechogenic small intestine with short femurs. Subsequent pregnancy MTOP after antenatal USS showed hygroma coli, ascites, short femurs, double outlet right ventricle. Genomic sequencing on stored fetal DNA samples confirmed homozygous UROS p.Cys73Arg variants in both fetuses.

PMID 15065102 Lazebnik et al 2004 reported the prenatal findings of two siblings with CEP secondary to homozygous pathogenic C73R variants. 1st child - USS at 17.5 weeks gestation showed increased nuchal thickness (9.7mm) with mild ascites, pericardial effusion, and skin oedema which persisted on subsequent scans. 2nd child - 16 week USS showed increased nuchal thickness (8.7mm) with scalp oedema, ascites, pericardial effusion, skin oedema and hepatomegaly.

Other cases with antenatal features, particularly non-immune hydrops, secondary to suspected CEP reported but not confirmed molecularly.
Sources: Literature
Fetal anomalies v0.2172 Zornitza Stark removed gene:UROS from the panel
Fetal anomalies v0.1871 UROS Zornitza Stark Phenotypes for gene: UROS were changed from CONGENITAL ERYTHROPOIETIC PORPHYRIA to Porphyria, congenital erythropoietic, MIM# 263700
Fetal anomalies v0.1870 UROS Zornitza Stark Publications for gene: UROS were set to
Fetal anomalies v0.1866 UROS Alison Yeung Marked gene: UROS as ready
Fetal anomalies v0.1866 UROS Alison Yeung Gene: uros has been classified as Red List (Low Evidence).
Fetal anomalies v0.1866 UROS Alison Yeung Classified gene: UROS as Red List (low evidence)
Fetal anomalies v0.1866 UROS Alison Yeung Added comment: Comment on list classification: fetal anomalies not a typical finding.
Fetal anomalies v0.1866 UROS Alison Yeung Gene: uros has been classified as Red List (Low Evidence).
Fetal anomalies v0.1865 UROS Alison Yeung reviewed gene: UROS: Rating: RED; Mode of pathogenicity: None; Publications: 24027798, 12533808; Phenotypes: PORPHYRIA, CONGENITAL ERYTHROPOIETIC (MIM #263700); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.1784 LRAT Daniel Flanagan reviewed gene: LRAT: Rating: RED; Mode of pathogenicity: None; Publications: 11381255, 18055821, 22570351, 17011878, 29973277, 24625443, 22559933, 31448181; Phenotypes: Leber congenital amaurosis 14 MIM#613341, Retinal dystrophy, early-onset severe MIM#613341, Retinitis pigmentosa, juvenile MIM#613341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1464 AIPL1 Zornitza Stark Phenotypes for gene: AIPL1 were changed from LEBER CONGENITAL AMAUROSIS 4 to Leber congenital amaurosis 4, 604393; Cone-rod dystrophy, 604393; Retinitis pigmentosa, juvenile, 604393
Fetal anomalies v0.1461 AIPL1 Zornitza Stark reviewed gene: AIPL1: Rating: RED; Mode of pathogenicity: None; Publications: 10615133; Phenotypes: Leber congenital amaurosis 4, 604393, Cone-rod dystrophy, 604393, Retinitis pigmentosa, juvenile, 604393; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.935 ZNF750 Chloe Stutterd reviewed gene: ZNF750: Rating: RED; Mode of pathogenicity: None; Publications: Smit, C., Bütow, K. W., Naidoo, S., & Olorunju, S. (2019). Identification of Possible Maternal Risk Factors for Development of Syndromic Oro-Facial Clefts. Clinical Neurology and Neuroscience, 3(3), 58.; Phenotypes: 610227; Mode of inheritance: None
Fetal anomalies v0.426 CEP290 Zornitza Stark Phenotypes for gene: CEP290 were changed from LEBER CONGENITAL AMAUROSIS TYPE 10; BARDET-BIEDL SYNDROME TYPE 14; JOUBERT SYNDROME TYPE 5; SENIOR-LOKEN SYNDROME TYPE 6; MECKEL SYNDROME TYPE 4 to Bardet-Biedl syndrome 14, MIM# 615991; Joubert syndrome 5, MIM# 610188; Meckel syndrome 4, MIM# 611134
Fetal anomalies v0.0 RPGRIP1 Zornitza Stark gene: RPGRIP1 was added
gene: RPGRIP1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RPGRIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPGRIP1 were set to CONE-ROD DYSTROPHY 13; LEBER CONGENITAL AMAUROSIS 6
Fetal anomalies v0.0 RPE65 Zornitza Stark gene: RPE65 was added
gene: RPE65 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RPE65 were set to LEBER CONGENITAL AMAUROSIS
Fetal anomalies v0.0 NMNAT1 Zornitza Stark gene: NMNAT1 was added
gene: NMNAT1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: NMNAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NMNAT1 were set to LEBER CONGENITAL AMAUROSIS
Fetal anomalies v0.0 CRX Zornitza Stark gene: CRX was added
gene: CRX was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CRX was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CRX were set to CRX-RELATED LEBER CONGENITAL AMAUROSIS LEBER CONGENITAL AMAUROSIS 7
Fetal anomalies v0.0 CRB1 Zornitza Stark gene: CRB1 was added
gene: CRB1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CRB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CRB1 were set to RETINITIS PIGMENTOSA-12, AUTOSOMAL RECESSIVE; LEBER CONGENITAL AMAUROSIS 8
Fetal anomalies v0.0 AIPL1 Zornitza Stark gene: AIPL1 was added
gene: AIPL1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: AIPL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AIPL1 were set to LEBER CONGENITAL AMAUROSIS 4
Fetal anomalies v0.0 LRAT Zornitza Stark gene: LRAT was added
gene: LRAT was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: LRAT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRAT were set to LEBER CONGENITAL AMAUROSIS
Fetal anomalies v0.0 UROS Zornitza Stark gene: UROS was added
gene: UROS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UROS were set to CONGENITAL ERYTHROPOIETIC PORPHYRIA
Fetal anomalies v0.0 CEP290 Zornitza Stark gene: CEP290 was added
gene: CEP290 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CEP290 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CEP290 were set to LEBER CONGENITAL AMAUROSIS TYPE 10; BARDET-BIEDL SYNDROME TYPE 14; JOUBERT SYNDROME TYPE 5; SENIOR-LOKEN SYNDROME TYPE 6; MECKEL SYNDROME TYPE 4