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| Mendeliome v0.10576 | AARS | Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Spastic paraplegia 85, autosomal recessive, MIM# 619686; Ataxia, sensory, 1, autosomal dominant, MIM# 608984; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10572 | AARS | Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053; Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10571 | AARS | Zornitza Stark Publications for gene: AARS were set to 28493438; 25817015; 20045102; 22009580; 22206013; 30373780; 26032230; 33909043 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.10570 | AARS | Zornitza Stark edited their review of gene: AARS: Added comment: PMID 31775912: single multigenerational family with leukoencephalopathy segregating AARS1 variant.; Changed publications: 28493438, 25817015, 20045102, 22009580, 22206013, 30373780, 26032230, 31775912; Changed phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339, Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287, Leukoencephalopathy, hereditary diffuse, with spheroids 2, MIM# 619661 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9351 | AARS | Zornitza Stark Phenotypes for gene: AARS were changed from Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287 to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; trichothiodystrophy, MONDO:0018053 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9350 | AARS | Zornitza Stark Publications for gene: AARS were set to 28493438; 25817015; 20045102; 22009580; 22206013; 30373780; 26032230 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9347 | AARS | Eleanor Williams changed review comment from: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB. Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family.; to: PMID: 33909043 - Botta et al 2021 - using WES or WGS analysis of 34 unsolved cases with multi-system phenotypes, but with hair alterations that are typical of trichothiodystrophy but no reported photosensitivity, they identified 2 unrelated cases carrying 4 potentially pathogenic variants in the AARS1 gene (previously known as AARSB. Both patients had very rare compound heterozygous missense variants. In one family there was an older affected sibling but segregation data was not available for either family. Functional studies suggest that the variants affects gene product stability. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.9347 | AARS | Eleanor Williams reviewed gene: AARS: Rating: ; Mode of pathogenicity: None; Publications: 33909043; Phenotypes: trichothiodystrophy, MONDO:0018053; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8897 | FGD1 | Zornitza Stark Phenotypes for gene: FGD1 were changed from to Aarskog-Scott syndrome, MIM # 305400; Mental retardation, X-linked syndromic 16, MIM# 305400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.8894 | FGD1 | Zornitza Stark reviewed gene: FGD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 7954831, 20082460; Phenotypes: Aarskog-Scott syndrome, MIM # 305400, Mental retardation, X-linked syndromic 16, MIM# 305400; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4002 | AARS2 | Zornitza Stark Marked gene: AARS2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4002 | AARS2 | Zornitza Stark Gene: aars2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4002 | AARS2 | Zornitza Stark Phenotypes for gene: AARS2 were changed from to Combined oxidative phosphorylation deficiency 8 MIM#614096; Leukoencephalopathy, progressive, with ovarian failure MIM#615889; MONDO:0013570 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4001 | AARS2 | Zornitza Stark Publications for gene: AARS2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.4000 | AARS2 | Zornitza Stark Mode of inheritance for gene: AARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3999 | AARS2 | Zornitza Stark edited their review of gene: AARS2: Changed phenotypes: Combined oxidative phosphorylation deficiency 8 MIM#614096, Leukoencephalopathy, progressive, with ovarian failure MIM#615889, MONDO:0013570 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3999 | AARS2 | Zornitza Stark reviewed gene: AARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 30706699, 27839525, 21549344, 25058219, 24808023; Phenotypes: Combined oxidative phosphorylation deficiency 8 MIM#614096, Leukoencephalopathy, progressive, with ovarian failure MIM#615889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3999 | AARS | Zornitza Stark Marked gene: AARS as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3999 | AARS | Zornitza Stark Gene: aars has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3999 | AARS | Zornitza Stark Phenotypes for gene: AARS were changed from to Epileptic encephalopathy, early infantile, 29, MIM# 616339; Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3998 | AARS | Zornitza Stark Publications for gene: AARS were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3997 | AARS | Zornitza Stark Mode of inheritance for gene: AARS was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3996 | AARS | Zornitza Stark reviewed gene: AARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 28493438, 25817015, 20045102, 22009580, 22206013, 30373780, 26032230; Phenotypes: Epileptic encephalopathy, early infantile, 29, MIM# 616339, Charcot-Marie-Tooth disease, axonal, type 2N, MIM# 613287; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v0.3643 | NARS |
Zornitza Stark gene: NARS was added gene: NARS was added to Mendeliome. Sources: Literature Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: NARS were set to 32738225 Phenotypes for gene: NARS were set to Abnormal muscle tone; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Ataxia; Abnormality of the face; Demyelinating peripheral neuropathy Review for gene: NARS was set to GREEN Added comment: [Please note that HGNC Approved Gene Symbol for this gene is NARS1] Manole et al (2020 - PMID: 32738225) provide evidence that both biallelic and monoallelic (de novo) pathogenic NARS1 variants cause a neurodevelopmental disorder. In total 32 individuals from 21 families are reported, with biallelic variants identified in individuals from 13 families and de novo in 8 families. Similar features were reported for AR/AD occurrences of the disorder and included microcephaly (90% - most often primary), epilepsy (23/32 or 74% - variable semiology incl. partial/myoclonic/generalized tonic-clonic seizures), DD and ID (as a universal feature), abnormal tone in several (hypotonia/spasticity), ataxia, demyelinating peripheral neuropathy (in 3 or more for each inheritance mode - or a total of 25%). Some individuals had dysmorphic features. NARS1 encodes an aminoacyl-tRNA synthetase (ARS) [asparaginyl-tRNA synthetase 1]. Aminoacyl-tRNA synthetases constitute a family of enzymes catalyzing attachment of amino-acids to their cognate tRNAs. As the authors comment, mutations in genes encoding several other ARSs result in neurological disorders ranging from peripheral neuropathy to severe multi-systemic NDD. Dominant, recessive or both modes for inheritance for mutations in the same gene (e.g. AARS1, YARS1, MARS1, etc) have been reported. Some variants were recurrent, e.g. the c.1600C>T / p.Arg534* which occurred in 6 families as a de novo event or c.1633C>T p.Arg545Cys (homozygous in 6 families). 3 different variants were reported to have occured de novo (c.965G>T - p.Arg322Leu, c.1525G>A - p.Gly509Ser, p.Arg534*) with several other variants identified in hmz/compound htz individuals. A single SNV (c.1067A>C - p.Asp356Ala) was suggested to be acting as modifier and pathogenic only when in trans with a severe variant. [NM_004539.4 used as RefSeq for all]. The authors provide several lines of evidence for a partial loss-of-function effect (e.g. reduction in mRNA expression, enzyme levels and activity in fibroblasts or iNPCs) underlying pathogenicity of the variants identified in individuals with biallelic variants. A gain-of-function (dominant-negative) effect is proposed for de novo variants (such effect also demonstrated for the p.Arg534* in a zebrafish model). Sources: Literature |
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| Mendeliome v0.0 | AARS2 |
Zornitza Stark gene: AARS2 was added gene: AARS2 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: AARS2 was set to Unknown |
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| Mendeliome v0.0 | AARS |
Zornitza Stark gene: AARS was added gene: AARS was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: AARS was set to Unknown |
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