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| BabyScreen+ newborn screening v0.2063 | SERPING1 |
Lilian Downie gene: SERPING1 was added gene: SERPING1 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: SERPING1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SERPING1 were set to PMID: 32898710 Phenotypes for gene: SERPING1 were set to Angioedema, hereditary, 1 and 2 MIM#106100 Review for gene: SERPING1 was set to RED Added comment: episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. Age of onset not typically <5 Treatment Purified C1 inhibitor concentrate (Cinryze, Berinert, HAEGARDA, or Ruconest), Ecallantide (Kalbitor), Icatibant (Firazyr), Lanadelumab, Orladeyo (berotralstat), FFP or solvent-detergent treated plasma, antisense oligonucleotide treatment (donidalorsen) Sources: Expert list |
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| BabyScreen+ newborn screening v0.2063 | SOX3 |
Lilian Downie gene: SOX3 was added gene: SOX3 was added to Baby Screen+ newborn screening. Sources: Expert list Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SOX3 were set to PMID: 31678974, PMID: 15800844 Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked MIM#312000 Review for gene: SOX3 was set to AMBER Added comment: Amber in our mendeliome - reviewed for ID Green in pituitary disorders Xq27.1 duplication most common mechanism - inclusion might be a question of whether we can detect CNV's in this region neonatal hypoglycemia and growth hormone deficiency in addition to variable deficiencies of other pituitary hormones. Brain hypoplasia of the anterior pituitary with hypoplasia or absence of the lower half of the infundibulum Rx Growth hormone, levothyroxine, hydrocortisone Sources: Expert list |
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| BabyScreen+ newborn screening v0.1977 | HSD11B2 |
Zornitza Stark gene: HSD11B2 was added gene: HSD11B2 was added to Baby Screen+ newborn screening. Sources: Expert list treatable, endocrine tags were added to gene: HSD11B2. Mode of inheritance for gene: HSD11B2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: HSD11B2 were set to Apparent mineralocorticoid excess, MIM# 218030; MONDO:0009025 Review for gene: HSD11B2 was set to GREEN Added comment: Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone. More than 10 unrelated families reported. Onset is usually in infancy or early childhood. Non-genetic confirmatory testing: aldosterone, renin, potassium levels Sources: Expert list |
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| BabyScreen+ newborn screening v0.1975 | HOGA1 |
Zornitza Stark gene: HOGA1 was added gene: HOGA1 was added to Baby Screen+ newborn screening. Sources: Expert list treatable, metabolic tags were added to gene: HOGA1. Mode of inheritance for gene: HOGA1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HOGA1 were set to 20797690; 21896830; 22391140 Phenotypes for gene: HOGA1 were set to Hyperoxaluria, primary, type III MIM#613616 Review for gene: HOGA1 was set to GREEN Added comment: Well-established association with primary hyperoxaluria type III. c.700+5G>T is a recurrent pathogenic variant in European populations (possibly founder) and has high frequency in gnomad (0.2-0.3%). Onset in infancy, progressive multi-system disorder. Treatment: pyridoxine, drinking large volumes, alkalinzation of urine, pyrophosphate-containing solutions, liver-kidney transplant Non-genetic confirmatory testing: urinary oxalate 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 v0.1621 | PRF1 |
Zornitza Stark changed review comment from: Treatment: Emapalumab, bone marrow transplant; to: Well established gene-disease association. Onset is generally in infancy or early childhood. Treatment: Emapalumab, bone marrow transplant. Non-genetic confirmatory tests: natural killer cell activity, cytotoxic T lymphocyte activity |
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| BabyScreen+ newborn screening v0.1521 | STXBP2 |
Seb Lunke changed review comment from: Established gene-disease association. Childhood onset, multi-system disorder Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity; to: Established gene-disease association. Childhood onset, hyperinflammatory disorder Treatment: Emapalumab ,Hematopoietic stem cell transplantation (HSCT) - bone marrow transplant Non-genetic confirmatory test: natural killer cell activity, cytotoxic T lymphocyte activity |
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| BabyScreen+ newborn screening v0.1456 | REN |
Zornitza Stark changed review comment from: Established gene-disease association. Presents as fetal anuria leading to perinatal death. No specific treatment.; to: Established gene-disease association. Bi-allelic LOF variants cause renal tubular dysgenesis, which presents as fetal anuria leading to perinatal death.. Mono-allelic variants, likely through a different mechanism (mostly missense) cause tubulointerstitial disease. More severe phenotype associated with variants that are located in the protein leader peptide and affecting its co-translational insertion in the endoplasmic reticulum (ER). No specific treatment for either. |
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| BabyScreen+ newborn screening v0.0 | LUM |
Zornitza Stark gene: LUM was added gene: LUM was added to gNBS. Sources: Expert Review Red,BabySeq Category C gene Mode of inheritance for gene: LUM was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: LUM were set to Amyotrophic lateral sclerosis |
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