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| Fetal anomalies v1.67 | NODAL |
Zornitza Stark edited their review of gene: NODAL: Added comment: NODAL is a good biological candidate for heterotaxy disorders, and this is supported by animal models. The gene is depleted for LoF variants in gnomad. The missense variants reported in PMIDs 9354794 and 19064609 are present at a high population frequency in gnomad, including some in homozygous case: their association with disease is DISPUTED. A total of at least 7 families reported with severe CHD and high impact variants (stop gain, frameshift and canonical splice site). However, almost invariably these were inherited from unaffected or questionably affected parents (e.g. self reports of heart murmur in childhood), raising questions about whether these variants contribute to disease under a monogenic or polygenic model and/or about penetrance. Discussed at GenCC on 13/9/2022 and agreed on MODERATE assessment.; Changed rating: AMBER; Changed publications: 9354794, 19064609, 29368431, 19933292, 11311163, 30293987 |
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| Fetal anomalies v0.4180 | MIA3 |
Chirag Patel gene: MIA3 was added gene: MIA3 was added to Fetal anomalies. Sources: Expert list Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MIA3 were set to PMID: 32101163, 33778321 Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269 Review for gene: MIA3 was set to AMBER Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization. Can present with IUGR antenatally. Suitable for fetal anomalies panel. Sources: Expert list |
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| Fetal anomalies v0.3756 | TPO |
Krithika Murali gene: TPO was added gene: TPO was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TPO was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPO were set to 34220711; 30662777 Phenotypes for gene: TPO were set to Thyroid dyshormonogenesis 2A - MIM#274500 Review for gene: TPO was set to GREEN Added comment: Well-established association with thyroid dyshormonogenesis. 3 affected individuals from 2 unrelated families reported with fetal goitre. 34220711 Rodrigues et al 2021 - report 2 siblings who were diagnosed with fetal goitre on antenatal ultrasound at 26 and 32 weeks gestation. Pathogenic compound het TPO variants identified inherited from unaffected carrier parents. 30662777 - report a proband diagnosed with fetal goitre at 29 weeks gestation. Compound heterozygous TPO variants identified. Sources: Literature |
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| Fetal anomalies v0.3722 | TG |
Krithika Murali gene: TG was added gene: TG was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TG were set to 33832185; 19169491; 28620499; 18631008; 12915634 Phenotypes for gene: TG were set to Thyroid dyshormonogenesis 3 - MIM#274700 Review for gene: TG was set to GREEN Added comment: Well-established gene-disease association with congenital hypothyroidism and fetal goitre. Sources: Literature |
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| Fetal anomalies v0.3722 | SLC5A5 |
Krithika Murali gene: SLC5A5 was added gene: SLC5A5 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: SLC5A5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC5A5 were set to 34806438; 34726525; 33815280; 32805706; 31115276 Phenotypes for gene: SLC5A5 were set to Thyroid dyshormonogenesis 1 - MIM#274400 Review for gene: SLC5A5 was set to GREEN Added comment: Biallelic variants associated with congenital hypothyroidism. PMID 32805706 Stoupa et al 2020 report an affected male with antenatal goitre diagnosed at 25 weeks gestation and treated with intraamniotic levothyroxine injections. Sources: Literature |
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| Fetal anomalies v0.3709 | IYD |
Krithika Murali gene: IYD was added gene: IYD was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: IYD was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IYD were set to 18434651; 18765512; 838849; 14169503 Phenotypes for gene: IYD were set to Thyroid dyshormonogenesis 4 - MIM#274800 Review for gene: IYD was set to GREEN Added comment: Known association with congenital hypothyroidism secondary to thyroid dyshormonogenesis. Although antenatal diagnosis not reported, goitre known phenotypic feature. Sources: Literature |
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| Fetal anomalies v0.3709 | DUOXA2 |
Krithika Murali gene: DUOXA2 was added gene: DUOXA2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DUOXA2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DUOXA2 were set to Thyroid dyshormonogenesis 5, MIM# 274900 Review for gene: DUOXA2 was set to GREEN Added comment: Well-established gene disease association with congenital hypothyroidism Sources: Literature |
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| Fetal anomalies v0.3709 | DUOX2 |
Krithika Murali gene: DUOX2 was added gene: DUOX2 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: DUOX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DUOX2 were set to 33692749; 34019632; 34341225; 16134168 Phenotypes for gene: DUOX2 were set to Thyroid dyshormonogenesis 6 - MIM#607200 Review for gene: DUOX2 was set to GREEN Added comment: Well-established gene disease association with congenital hypothyroidism. Sources: Literature |
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| Fetal anomalies v0.3279 | ZBTB24 |
Krithika Murali gene: ZBTB24 was added gene: ZBTB24 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ZBTB24 were set to 32865561; 21596365; 29023266; 32061411; 21906047; 28128455; 23739126; 22786748 Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069 Review for gene: ZBTB24 was set to GREEN Added comment: Well reported association with ICF2 (immunodeficiency-centromeric instability facial anomalies syndrome 2). Patients have immunodeficiency (mainly hypo/agammaglobulinemia in the presence of B cells), recurrent infections (namely respiratory and gastrointestinal) and dysmorphic facies. Although antenatal features not thoroughly described for published cases, low birth weight has been a reported feature as well as hypertelorism and micrognathia/retrognathia - these have the potential to be detected prenatally. PMID 32865561 Helfricht et al 2020 - "loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance". PMID 32061411 Banday. et al 2020 - report a patient with this condition and granulomatous hepatitis. Review phenotype of previously reported patients, low birth weight and facial dysmorphism including micrognathia noted in other cases. PMID 29023266 Conrad et al 2017 - describe a 17 month old boy with recurrent infections, growth failure, facial anomalies (including hyperterlorism/low set ears), and inflammatory bowel disease. No antenatal information. PMID 28128455 van den Boogaard 2017 - 5 new patients described PMID 23739126 Nitta et al 2013 - report 3 unrelated patients, x1 patient - lower birth weight and head circumference. At age 5 had macrocephaly, hyperterlorism. Noted to have bilateral hydronephrosis. x1 patient BW 2660g, micrognathia, hyperterlorism. PMID 21906047 Chouery et al 2012 - 3 siblings from a Lebanese family with novel homozygous LoF variant. Apparently normal pregnancies, at time of diagnostic assessment HC between the 5th and 15th centiles, height below the 5th percentile. Dysmorphic features including high arched palate, small chin, retrognathism and everted lower lips. PMID 22786748 Cerbone et al 2012 - report an 8 year old M of consanguineous Moroccan ancestry with ID, dysmorphic features, cafe au last macules and a large arachnoid cyst in the right temporal region, causing compression of the temporal lobe and lateral ventricle PMID 21596365 de Greef et al 2011 - report 4 new unrelated patients, no antenatal information Sources: Literature |
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| Fetal anomalies v0.3151 | PLEKHA5 |
Krithika Murali gene: PLEKHA5 was added gene: PLEKHA5 was added to Fetal anomalies. Sources: Literature,Expert list Mode of inheritance for gene: PLEKHA5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PLEKHA5 were set to 29805042 Phenotypes for gene: PLEKHA5 were set to cleft lip; cleft palate Review for gene: PLEKHA5 was set to AMBER Added comment: No new published evidence since last PanelApp review April 2020 --- One de novo variant reported, another 5 '3C' rare variants reported in 6 families in this cohort; unclear if monogenic or polygenic contribution to CL/P. Sources: Literature, Expert list |
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| Fetal anomalies v0.3117 | PLG | Zornitza Stark Phenotypes for gene: PLG were changed from Plasminogen deficiency, type I, OMIM:217090; Dysplasminogenemia, OMIM:217090 to Plasminogen deficiency, type I, MIM# 217090; Hydrocephalus | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1249 | NOG | Zornitza Stark Marked gene: NOG as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1249 | NOG | Zornitza Stark Gene: nog has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1249 | NOG | Zornitza Stark Phenotypes for gene: NOG were changed from SYMPHALANGISM PROXIMAL SYNDROME; TARSAL-CARPAL COALITION SYNDROME; MULTIPLE SYNOSTOSES SYNDROME TYPE 1; BRACHYDACTYLY TYPE B2; STAPES ANKYLOSIS WITH BROAD THUMB AND TOES to Brachydactyly, type B2 (MIM#611377); Multiple synostoses syndrome 1 (MIM#186500); Stapes ankylosis with broad thumbs and toes (MIM#184460); Symphalangism, proximal, 1A (MIM#185800); Tarsal-carpal coalition syndrome (MIM#186570) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1248 | NOG | Zornitza Stark Publications for gene: NOG were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1247 | NOG | Zornitza Stark Mode of inheritance for gene: NOG was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1246 | NOG | Zornitza Stark Classified gene: NOG as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1246 | NOG | Zornitza Stark Gene: nog has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1240 | NOG | Daniel Flanagan reviewed gene: NOG: Rating: AMBER; Mode of pathogenicity: None; Publications: 11846737, 18440889, 12089654, 10080184, 15066478, 22088931, 17381491; Phenotypes: Brachydactyly, type B2 (MIM#611377), Multiple synostoses syndrome 1 (MIM#186500), Stapes ankylosis with broad thumbs and toes (MIM#184460), Symphalangism, proximal, 1A (MIM#185800), Tarsal-carpal coalition syndrome (MIM#186570); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.886 | TNFRSF11A |
Krithika Murali gene: TNFRSF11A was added gene: TNFRSF11A was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TNFRSF11A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TNFRSF11A were set to 18606301; 32048120 Phenotypes for gene: TNFRSF11A were set to Osteopetrosis, autosomal recessive 7 - MIM# 612301 Review for gene: TNFRSF11A was set to AMBER Added comment: 8 patients from 7 unrelated families with severe osteoclast-poor osteopetrosis with homozygosity or compound heterozygosity for 7 different variants. The condition is associated with a defect in immunoglobulin production. Although antenatal diagnosis not specifically reported for this gene, diagnosis of severe osteopetrosis antenatally and during early infancy has been reported, including cases with no causative variants identified (PMID 23085203) Sources: Literature |
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| Fetal anomalies v0.0 | SLC5A5 |
Zornitza Stark gene: SLC5A5 was added gene: SLC5A5 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: SLC5A5 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SLC5A5 were set to THYROID HORMONOGENESIS DEFECT I |
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| Fetal anomalies v0.0 | DSPP |
Zornitza Stark gene: DSPP was added gene: DSPP was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: DSPP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DSPP were set to DENTINOGENESIS IMPERFECTA, SHIELDS TYPE II; DEAFNESS AUTOSOMAL DOMINANT TYPE 39 WITH DENTINOGENESIS IMPERFECTA 1 |
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| Fetal anomalies v0.0 | DOCK8 |
Zornitza Stark gene: DOCK8 was added gene: DOCK8 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp Mode of inheritance for gene: DOCK8 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DOCK8 were set to HYPERIMMUNOGLOBULIN E RECURRENT INFECTION SYNDROME AUTOSOMAL RECESSIVE |
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| Fetal anomalies v0.0 | PLG |
Zornitza Stark gene: PLG was added gene: PLG was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: PLG was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PLG were set to Plasminogen deficiency, type I, OMIM:217090; Dysplasminogenemia, OMIM:217090 |
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| Fetal anomalies v0.0 | KIF14 |
Zornitza Stark gene: KIF14 was added gene: KIF14 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: KIF14 were set to 29343805; 24128419; 30388224; 28892560 Phenotypes for gene: KIF14 were set to Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome, MONDO:0014552; Microcephaly 20, primary, autosomal recessive, OMIM:617914; Meckel syndrome 12, OMIM:616258; Microcephaly 20, primary, autosomal recessive, MONDO:0054761 |
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| Fetal anomalies v0.0 | NOG |
Zornitza Stark gene: NOG was added gene: NOG was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp Mode of inheritance for gene: NOG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: NOG were set to SYMPHALANGISM PROXIMAL SYNDROME; TARSAL-CARPAL COALITION SYNDROME; MULTIPLE SYNOSTOSES SYNDROME TYPE 1; BRACHYDACTYLY TYPE B2; STAPES ANKYLOSIS WITH BROAD THUMB AND TOES |
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