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| Mendeliome v1.2550 | KEL | Zornitza Stark Phenotypes for gene: KEL were changed from [Blood group, Kell] 110900 to vein of Galen aneurysm, MONDO:0015196 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2547 | KEL | Zornitza Stark reviewed gene: KEL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: vein of Galen aneurysm, MONDO:0015196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2499 | KEL | Achchuthan Shanmugasundram reviewed gene: KEL: Rating: AMBER; Mode of pathogenicity: None; Publications: 30578106, 37978175; Phenotypes: vein of Galen aneurysm, MONDO:0015196; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1685 | GALE | Zornitza Stark Phenotypes for gene: GALE were changed from Galactose epimerase deficiency MIM#230350; Disorders of galactose metabolism to Galactose epimerase deficiency MIM#230350; Thrombocytopenia 12, syndromic, MIM#620776 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1684 | GALE | Zornitza Stark Publications for gene: GALE were set to 27604308; 9700591 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1683 | GALE | Zornitza Stark reviewed gene: GALE: Rating: GREEN; Mode of pathogenicity: None; Publications: 30247636, 34159722, 36395340; Phenotypes: Thrombocytopenia 12, syndromic, MIM#620776; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1262 | MYCN | Elena Savva Phenotypes for gene: MYCN were changed from Feingold syndrome 1; megalencephaly; ventriculomegaly; hypoplastic corpus callosum; intellectual disability; polydactyly; neuroblastoma to Neurodevelopmental disorder (MONDO:0700092), MYCN-related; Feingold syndrome 1 MIM#164280 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1077 | AQP4 | Zornitza Stark Phenotypes for gene: AQP4 were changed from ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 to Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1071 | AQP4 |
Lucy Spencer gene: AQP4 was added gene: AQP4 was added to Mendeliome. Sources: Literature Mode of inheritance for gene: AQP4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AQP4 were set to 37143309 Phenotypes for gene: AQP4 were set to ?Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting MIM#620448 Review for gene: AQP4 was set to AMBER Added comment: PMID: 37143309 Cohort of patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). Missense variant in AQP4 seen homozygous in 2 siblings and het in the parents. Patients had macrocephaly, developmental delay, hypotonia, epilepsy, and cognitive deficit. Western blots on generated MDCK cell lines showed no detectable expression of AQP4 protein from the cells with the patients variant. Immunofluorescence also showed no membrane expression. Overexpression studies in HEK293T cells showed WT was seen as mainly monomers or dimers where as variant protein formed large aggregates- likely due to the saturation of protein degradation pathways because of the overexpression. Sources: Literature |
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| Mendeliome v1.1071 | GPRC5B |
Lucy Spencer gene: GPRC5B was added gene: GPRC5B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GPRC5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GPRC5B were set to 37143309 Phenotypes for gene: GPRC5B were set to Megalencephalic leukoencephalopathy with subcortical cysts 3 620447 Review for gene: GPRC5B was set to GREEN Added comment: PMID: 37143309 Cohort of 5 patients with an MRI based diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC). 3 unrelated patients had variants in GPRC5B, 2 have the same inframe dup Ile175dup and the third has an in frame dup of Ala177. All 3 were de novo and unaffected siblings did not have the variants. All patients have macrocephaly, delayed motor development, seizures, all had varying degrees of cognitive deficits. 2 also had spasticity, ataxia and dystonia. MRI showed MLC, abnormal and swollen cerebral white matter. Patient cell lines showed reduced regulatory volume decrease, and western blot showed a strong increase in GRPC5B levels in patient lymphoblasts. Together, these findings indicate disturbed volume regulation in lymphoblasts from patients with GPRC5B variants, potentially due to increased GPRC5B levels. Transfected cells caused increased volume-regulated anion channel activity. Sources: Literature |
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| Mendeliome v1.343 | GALE | Zornitza Stark Tag treatable tag was added to gene: GALE. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13596 | HEPACAM | Zornitza Stark Phenotypes for gene: HEPACAM were changed from to Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925; Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13593 | HEPACAM | Zornitza Stark reviewed gene: HEPACAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 21419380, 21419380; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts 2A, MIM# 613925, Megalencephalic leukoencephalopathy with subcortical cysts 2B, remitting, with or without mental retardation, MIM# 613926; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13398 | PIK3CA | Zornitza Stark Phenotypes for gene: PIK3CA were changed from to Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501; CLAPO syndrome, somatic, MIM# 613089; CLOVE syndrome, somatic, MIM# 612918 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13396 | PIK3CA | Zornitza Stark reviewed gene: PIK3CA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-capillary malformation (MCAP) syndrome , MIM#602501, CLAPO syndrome, somatic, MIM# 613089, CLOVE syndrome, somatic, MIM# 612918; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13367 | PIK3R2 | Zornitza Stark Phenotypes for gene: PIK3R2 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.13364 | PIK3R2 | Zornitza Stark reviewed gene: PIK3R2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22729224, 23745724, 33604570; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM# 603387; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12316 | AKT3 | Elena Savva Phenotypes for gene: AKT3 were changed from to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MIM#615937 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.12314 | AKT3 | Elena Savva reviewed gene: AKT3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 22729224; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 MIM#615937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11044 | RNASET2 | Zornitza Stark Phenotypes for gene: RNASET2 were changed from to Leukoencephalopathy, cystic, without megalencephaly MIM#612951 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.11011 | RNASET2 | Ain Roesley reviewed gene: RNASET2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31349848, 19525954, 27091087, 29336640, 18545798, 15851732; Phenotypes: Leukoencephalopathy, cystic, without megalencephaly MIM#612951; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10656 | STRADA | Zornitza Stark Phenotypes for gene: STRADA were changed from to Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087; Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10653 | STRADA | Zornitza Stark reviewed gene: STRADA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17522105, 27170158, 28688840; Phenotypes: Polyhydramnios, megalencephaly, and symptomatic epilepsy, OMIM:611087, Polyhydramnios, megalencephaly, and symptomatic epilepsy, MONDO:0012611; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10561 | CCND2 | Alison Yeung Phenotypes for gene: CCND2 were changed from to Neurodevelopmental disorder, CCND2-related MONDO: 0700092; Microcephaly, MONDO: 0001149; Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3, MIM# 615938 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALE | Zornitza Stark Marked gene: GALE as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALE | Zornitza Stark Gene: gale has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10224 | GALE | Zornitza Stark Phenotypes for gene: GALE were changed from to Galactose epimerase deficiency MIM#230350; Disorders of galactose metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10223 | GALE | Zornitza Stark Publications for gene: GALE were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10216 | GALE | Zornitza Stark Mode of inheritance for gene: GALE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9823 | MLC1 | Zornitza Stark Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9779 | MLC1 | Daniel Flanagan reviewed gene: MLC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11254442, 18757878, 16652334; Phenotypes: Megalencephalic leukoencephalopathy with subcortical cysts (MIM#604004); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2620 | GALM |
Hazel Phillimore gene: GALM was added gene: GALM was added to Mendeliome. Sources: Literature Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to PMID: 30451973; 30910422 Phenotypes for gene: GALM were set to galactosaemia; type IV galactosaemia Review for gene: GALM was set to GREEN Added comment: Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422) Sources: Literature |
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| Mendeliome v0.2372 | MYCN | Zornitza Stark Phenotypes for gene: MYCN were changed from to Feingold syndrome 1; megalencephaly; ventriculomegaly; hypoplastic corpus callosum; intellectual disability; polydactyly; neuroblastoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2361 | MYCN | Ain Roesley reviewed gene: MYCN: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 21224895, 8470948, 30573562; Phenotypes: Feingold syndrome 1, megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, neuroblastoma; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.2361 | MYCN | Ain Roesley edited their review of gene: MYCN: Added comment: PMID: 30573562; case report of an individual with a missense in MYCN with functional studies done in neuronal progenitor/stem cells demonstrating gain-of-function; Changed rating: RED; Changed publications: PMID: 30573562; Changed phenotypes: megalencephaly, ventriculomegaly, hypoplastic corpus callosum, intellectual disability, polydactyly, neuroblastoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1537 | TBC1D7 | Zornitza Stark Phenotypes for gene: TBC1D7 were changed from to Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.1533 | TBC1D7 | Zornitza Stark reviewed gene: TBC1D7: Rating: AMBER; Mode of pathogenicity: None; Publications: 24515783, 23687350; Phenotypes: Macrocephaly/megalencephaly syndrome, autosomal recessive, MIM# 248000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.0 | GALE |
Zornitza Stark gene: GALE was added gene: GALE was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: GALE was set to Unknown |
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