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| BabyScreen+ newborn screening v1.114 | TUBB4B | Tommy Li Added phenotypes Leber congenital amaurosis with early-onset deafness MIM#617879 for gene: TUBB4B | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | DTHD1 | Tommy Li Added phenotypes Leber congenital amaurosis with myopathy for gene: DTHD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | CEP290 | Tommy Li Added phenotypes Senior-Loken syndrome 6, MIM# 610189; Meckel syndrome 4, MIM# 611134; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Bardet-Biedl syndrome 14, MIM# 615991 for gene: CEP290 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | UROS | Tommy Li Added phenotypes Porphyria, congenital erythropoietic MIM#263700 for gene: UROS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v1.114 | RPE65 | Tommy Li Added phenotypes Retinitis pigmentosa 20 MIM#613794; Leber congenital amaurosis 2 MIM#204100 for gene: RPE65 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.2148 | TUBB4B |
Lilian Downie gene: TUBB4B was added gene: TUBB4B was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBB4B were set to PMID: 29198720, 35240325 Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness MIM#617879 Review for gene: TUBB4B was set to RED Added comment: The TUBB4B gene has been associated with autosomal dominant Leber congenital amaurosis with early-onset deafness Not consistently hearing phenotype <5years therefore excluded Sources: Expert list |
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| BabyScreen+ newborn screening v0.1728 | RPE65 |
Zornitza Stark gene: RPE65 was added gene: RPE65 was added to gNBS. Sources: ClinGen for review, treatable, ophthalmological tags were added to gene: RPE65. Mode of inheritance for gene: RPE65 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: RPE65 were set to Leber congenital amaurosis 2 MIM#204100; Retinitis pigmentosa 20 MIM#613794 Review for gene: RPE65 was set to GREEN Added comment: Assessed as 'strong actionability' in paediatric patients by ClinGen. Biallelic RPE65 mutation-associated retinal dystrophy is a form of IRD caused by biallelic pathogenic variants in RPE65; it presents as a spectrum of disease with variable age of onset and progression of vision loss. Common clinical findings across the spectrum include night blindness, progressive loss of visual fields and loss of central vision. In LCA, night blindness often occurs from birth. Characteristically, these patients have residual cone-mediated vision in the first to third decades with progressive visual field loss until complete blindness is observed, most often in mid- to late-adulthood. A range of age of onset has been described for night blindness in RP, but it typically onsets in later childhood. In December 2017, the FDA approved LUXTURNA (voretigene neparvovec-rzyl) gene therapy for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The FDA’s conclusion of efficacy is based on improvement in a functional vision score over 1 year in a single open-label controlled Phase 3 study of 31 affected patients. The average age of the 31 randomized patients was 15 years (range 4 to 44 years), including 64% pediatric subjects (n=20, age from 4 to 17 years) and 36% adults (n=11). Functional vision was scored by a patient’s ability to navigate a course in various luminance levels. Using both treated eyes of the 21 subjects in the LUXTURNA treatment group, 11 (52%) had a clinically meaningful score improvement, while only one of the ten (10%) subjects in the control group had a clinically meaningful score improvement. Using the first treated eye only, 15/21 (71%) had a clinically meaningful score improvement, while no comparable score improvement was observed in controls. Other secondary clinical outcomes were also examined. Analysis of white light full-field light sensitivity threshold testing showed statistically significant improvement at 1 year in the LUXTURNA treatment group compared to the control group. The change in visual acuity was not significantly different between the LUXTURNA and control groups. LUXTURNA is administered subretinally by injection. Per the FDA package insert, the most common adverse reactions (incidence ≥ 5%) in the clinical trials for LUXTURNA included conjunctival hyperemia, cataract, increased intraocular pressure, retinal tear, dellen (thinning of the corneal stroma), and macular hole. Several other ocular adverse effects were also reported, including risk of endophthalmitis. Safety data was included on the basis of 41 patients (81 eyes). For review: availability of therapy? Sources: ClinGen |
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| BabyScreen+ newborn screening v0.1675 | UROS | John Christodoulou reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30685241; Phenotypes: hydros, photosensitivity, erythrodontia, corneal scarring, haemolytic anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1643 | UROS | Zornitza Stark Marked gene: UROS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1643 | UROS | Zornitza Stark Gene: uros has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1643 | UROS | Zornitza Stark Phenotypes for gene: UROS were changed from Porphyria, congenital erythropoietic to Porphyria, congenital erythropoietic MIM#263700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1642 | UROS | Zornitza Stark Publications for gene: UROS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.1641 | UROS |
Zornitza Stark Tag treatable tag was added to gene: UROS. Tag haematological tag was added to gene: UROS. |
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| BabyScreen+ newborn screening v0.627 | CEP290 | Zornitza Stark Phenotypes for gene: CEP290 were changed from Joubert syndrome to Bardet-Biedl syndrome 14, MIM# 615991; Joubert syndrome 5 610188; Leber congenital amaurosis 10, MIM# 611755; Meckel syndrome 4, MIM# 611134; Senior-Loken syndrome 6, MIM# 610189 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.625 | CEP290 | Zornitza Stark reviewed gene: CEP290: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bardet-Biedl syndrome 14, MIM# 615991, Joubert syndrome 5 610188, Leber congenital amaurosis 10, MIM# 611755, Meckel syndrome 4, MIM# 611134, Senior-Loken syndrome 6, MIM# 610189; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.606 | UROS | Lilian Downie reviewed gene: UROS: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 24027798; Phenotypes: Porphyria, congenital erythropoietic MIM#263700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| BabyScreen+ newborn screening v0.0 | DTHD1 |
Zornitza Stark gene: DTHD1 was added gene: DTHD1 was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: DTHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: DTHD1 were set to Leber congenital amaurosis with myopathy |
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| BabyScreen+ newborn screening v0.0 | UROS |
Zornitza Stark gene: UROS was added gene: UROS was added to gNBS. Sources: BabySeq Category A gene,Expert Review Green Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: UROS were set to Porphyria, congenital erythropoietic |
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