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| Ataxia and cerebellar anomalies - narrow panel v5.3 | ASL |
Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ASL. Tag Q4_23_NHS_review was removed from gene: ASL. |
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| Ataxia and cerebellar anomalies - narrow panel v5.3 | ASL | Sarah Leigh reviewed gene: ASL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v5.2 | ASL |
Achchuthan Shanmugasundram Source Expert Review Green was added to ASL. Source NHS GMS was added to ASL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Ataxia and cerebellar anomalies - narrow panel v4.49 | ASL |
Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 patients including 2 out of 7 patients with ataxia (patients 25 and 33, c.437G>A; c.446+1G>A and c.348+1G>A; c.532G>A respectively). Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective analysis of patients with ASA prior to March 2013 and then prospective analysis of patients until December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant (c.35G>A;p.(Arg12Gln), c.377G>A;p.(Arg126G1n) and c.1138A>G;p.(Lys380Glu) respectively. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries, PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 patients including 2 out of 7 patients with ataxia (patients 25 and 33, c.437G>A; c.446+1G>A and c.348+1G>A; c.532G>A respectively). Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective analysis of patients with ASA prior to March 2013 and then prospective analysis of patients until December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant (c.35G>A;p.(Arg12Gln), c.377G>A;p.(Arg126G1n) and c.1138A>G;p.(Lys380Glu) respectively. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ) |
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| Ataxia and cerebellar anomalies - narrow panel v4.49 | ASL |
Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 patients including 2 out of 7 patients with ataxia (patients 25 and 33, c.437G>A; c.446+1G>A and c.348+1G>A; c.532G>A respectively). Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective analysis of patients with ASA prior to March 2013 and then prospective analysis of patients until December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant (c.35G>A;p.(Arg12Gln), c.377G>A;p.(Arg126G1n) and c.1138A>G;p.(Lys380Glu) respectively. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ) |
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| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL |
Eleanor Williams Tag Q4_23_promote_green tag was added to gene: ASL. Tag Q4_23_NHS_review tag was added to gene: ASL. |
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| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL | Eleanor Williams changed review comment from: Comment on list classification: Promoting this gene to amber as there are 2 cases of patients with ataxia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023). Consulting with the Genomics England clinical team whether it would be appropriate to rate green.; to: Comment on list classification: Promoting this gene to amber with a recommendation for green rating as there are 5 cases of patients with ataxia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023 and PMID: 28251416 - Baruteau et al 2017). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL |
Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. Ataxia was first noticed at a median age of 8.5 years. The genotype was available for 19 patients, including 3 of those with Ataxia (patients 1, 4 and 14) each with a different homozygous missense variant. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ) |
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| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL |
Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ) |
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| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL |
Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not specifically mentioned as a phenotypic feature, although 7/50 patients were reported to show spasticity. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ) |
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| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL | Eleanor Williams Classified gene: ASL as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL | Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber as there are 2 cases of patients with ataxia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023). Consulting with the Genomics England clinical team whether it would be appropriate to rate green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.46 | ASL | Eleanor Williams Gene: asl has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.45 | ASL | Eleanor Williams Publications for gene: ASL were set to 38044746; 36994644; 28251416 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.44 | ASL | Eleanor Williams Phenotypes for gene: ASL were changed from Ataxia to Argininosuccinic aciduria, OMIM:207900; argininosuccinic aciduria, MONDO:0008815; Ataxia, HP:0001251 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.43 | ASL |
Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature. More recent retrospectives show that ataxia is reported in approx. 10% of individuals. 2 confirmed cases with ataxia and ASL variants are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy. The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g. PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA. PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients; c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. Ataxia is not mentioned as a phenotypic feature. More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported. PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53 years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 7 were reported to show ataxia and 4 of these individuals presented with ataxia by age 11 or less. Homozygous or compound het ASL variants were recorded in 25/60 paitents including 2 out of 7 patients with ataxia. Genotype data was not available for other patients. PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Ataxia was reported in 9 out of 52 patients studied. (PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ) |
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| Ataxia and cerebellar anomalies - narrow panel v4.43 | ASL | Eleanor Williams commented on gene: ASL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ataxia and cerebellar anomalies - narrow panel v4.40 | ASL |
Nour Elkhateeb gene: ASL was added gene: ASL was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ASL were set to 38044746; 36994644; 28251416 Phenotypes for gene: ASL were set to Ataxia Added comment: Ataxia has been reported in multiple individuals with argininosuccinic aciduria (PMID 38044746, 36994644, 28251416). Sources: Literature |
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| Ataxia and cerebellar anomalies - narrow panel v2.29 | ABCA2 |
Arina Puzriakova gene: ABCA2 was added gene: ABCA2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature Mode of inheritance for gene: ABCA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ABCA2 were set to 30237576; 29302074; 31047799 Phenotypes for gene: ABCA2 were set to Intellectual developmental disorder with poor growth and with or without seizures or ataxia, OMIM: 618808 Added comment: Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype. At least 7 individuals from 4 unrelated families reported at present with different biallelic variants in the ABCA2 gene. Overlapping clinical features include psychomotor delay (6/7), microcephaly (3/7), ataxia (3/7), and epilepsy (2/7). - Hu et al (PMID: 29302074) reported 3 sibs, of which one (III:2) was unable to walk and had ataxic gait. - Aslam and Naz (PMID: 31047799) provided clinical details on 2 siblings, both of whom presented delayed ambulation, staggered gait ataxia, limb incoordination and dysarthria, but no abnormalities on brain MRI. Sources: Literature |
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