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Leukodystrophy, adult onset v7.9 CTSA Luke Stuart changed review comment from: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys)). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 affected obligate carriers, from three pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.; to: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys)). This variant has been described across a number of CARASAL cohorts from varying backgrounds, though most patients described to-date are of European origin.

Hervé et al., 2012 (PMID 23175731): Identified a chromosome 20q13 region linked to a leukoencephalopathy phenotype in two French sisters. A later publication reported that this family was subsequently confirmed to carry the recurrent CTSA p.Arg325Cys variant (personal communication with the authors; 2026 report).

Bugiani et al., 2016 (PMID 27664989): First description of CARASAL in two Dutch kindreds. Haplotype analysis revealed a shared region of 1,145 kb on chromosome 20q13 suggesting a common ancestral origin, and the c.973C>T p.(Arg325Cys) variant (identified via exome sequencing) segregated with disease. The authors proposed that the introduced cysteine residue may alter protein folding, although SDS-PAGE experiments did not support this. Based on increased cathepsin A precursor protein, astrocytic endothelin-1 (ET-1) accumulation, increased premyelinating oligodendrocyte progenitors, and reduced myelin basic protein in patient white matter, they proposed that impaired ET-1 degradation contributes to vasculopathy and defective oligodendrocyte maturation. This mechanism is inferential and has not been experimentally validated.

Hwang et al., 2017 (PMID 28702507): Reported an additional British patient with CARASAL heterozygous for CTSA c.973C>T p(Arg325Cys). Analysis of the informative marker D20S838 suggested a common genetic ancestry with the previously reported Dutch families.

Budhdeo et al., 2022 (PMID 35904593): Described two further affected individuals, one of Chinese ancestry and one Brazilian individual of Italian origin, in who underwent exome sequencing and targeted Sanger sequencing, respectively. These cases expanded the ethnic distribution of CARASAL beyond the previously reported Dutch, British, and French families. Haplotype data were not available.

Cerfontaine et al., 2026 (PMID 41908989): Reported 21 affected individuals (including 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys), 4 affected obligate carriers) a from three Dutch pedigrees, including some overlap with the original 2016 Bugiani discovery cohort. The recurrent CTSA p.Arg325Cys variant was described as a Dutch founder variant and segregated with disease across multiple large pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI.

Yoon et al., 2023 (case report, accessed at:https://www.jns-journal.com/article/S0022-510X(23)01466-1/fulltext): Reported a Korean patient presenting with cognitive decline and leukodystrophy on brain imaging. Sequencing of a lysosomal disease panel identified heterozygous CTSA c.973C>T (p.Arg325Cys).

Population data:CTSA c.973C>T (p.Arg325Cys) is present in gnomAD v4 in one heterozygous individual (European non-Finnish ancestry), with no homozygotes observed (overall allele frequency 6.2 × 10^-7).
In silico data: AlphaMissense predicts the variant to be likely benign.

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Despite lacking functional evidence supporting variant pathogenicity and a yet-to-be determined disease mechanism, segregation and enrichment in relevant disease cohorts is convincing across multiple ethnic backgrounds. Thus a green rating is reiterated, with monoallelic inheritance.
Leukodystrophy, adult onset v7.9 CTSA Luke Stuart changed review comment from: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys)). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 affected obligate carriers, from two pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.; to: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys)). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 affected obligate carriers, from three pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.
Leukodystrophy, adult onset v7.9 CTSA Luke Stuart changed review comment from: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 obligate carriers, from two pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.; to: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys)). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 affected obligate carriers, from two pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.
Leukodystrophy, adult onset v7.9 CTSA Luke Stuart changed review comment from: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 obligate carriers. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.; to: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 obligate carriers, from two pedigrees. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.
Leukodystrophy, adult onset v7.9 CTSA Luke Stuart changed review comment from: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 obligate carriers. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.; to: CTSA is associated with autosmal dominant Brain small vessel disease 6 with leukoencephalopathy (OMIM:621394, accessed 08/2026), also referred to as Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL). CARASAL is caused by a single recurrent heterozygous CTSA variant, c.973C>T p.(Arg325Cys) (updated nomenclature NM_000308.4:c.919C>T p.(Arg307Cys). In a CARASAL case series comprising two families harboring heterozygous CTSA c.973C>T p.(Arg325Cys) identified by exome sequencing, haplotype analysis identified a shared region of 1,145 kb on chromosome 20q13 in affected individuals suggesting a common ancestor (Bugiani et al., 2016, PMID 27664989). N.B. all patients described to date are of European ancestry, aside from one Chinese proband described by Budheo et al., 2022 (PMID 35904593).

Cerfontaine et al., 2026 (PMID 41908989) described a large CARASAL case series comprising 16 patients heterozygous for CTSA c.973C>T p.(Arg325Cys) and 4 obligate carriers. The authors characterised CARASAL's defining leukodystrophy signature as a combination of very high, early, and progressive confluent white matter hyperintensity (particularly in the pons) with relatively mild associated atrophic changes. Pontine confluent white matter hyperintensities (WMHs) were present in 100% of patients (16/16), and extensive confluent WMHs present in 15/16 patients with MRI. The precise mechanism by which the CTSA c.973C>T p.(Arg325Cys) causes disease is largely unknown (Bugiani et al., 2016, PMID 27664989)

In conclusion, CARASAL, characterised by a prominent adult-onset leukodystrophy phenotype, is caused by a single recurrent heterozygous missense CTSA variant. Thus monoallelic inheritance is appropriate.
Leukodystrophy, adult onset v6.10 NOTCH3 Achchuthan Shanmugasundram commented on gene: NOTCH3: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v6.10 CST3 Achchuthan Shanmugasundram commented on gene: CST3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 RNASET2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 POLR1C Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 MARS Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 OCRL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 HMGCL Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toamberfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 RPS6KA3 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated toredfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v4.3 GCDH Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to greenand the mode of inheritance set to'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v3.18 SPG21 Sarah Leigh edited their review of gene: SPG21: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Leukodystrophy, adult onset v2.46 APP Sarah Leigh Tag Q1_23_promote_green was removed from gene: APP.
Leukodystrophy, adult onset v2.46 APP Sarah Leigh changed review comment from: The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 PSEN2 Sarah Leigh changed review comment from: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Amber and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 TTR Sarah Leigh commented on gene: TTR: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 PSEN2 Sarah Leigh edited their review of gene: PSEN2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: AMBER
Leukodystrophy, adult onset v2.46 PSEN1 Sarah Leigh commented on gene: PSEN1: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 PRNP Sarah Leigh commented on gene: PRNP: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 LAMB1 Sarah Leigh commented on gene: LAMB1: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 ITM2B Sarah Leigh commented on gene: ITM2B: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 GSN Sarah Leigh commented on gene: GSN: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 CST3 Sarah Leigh commented on gene: CST3: The rating of this gene has been updated to Amber and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v2.46 APP Sarah Leigh reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Leukodystrophy, adult onset v2.45 APP Sarah Leigh Source Expert Review Green was added to APP.
Source NHS GMS was added to APP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Leukodystrophy, adult onset v2.8 APP Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: APP.
Leukodystrophy, adult onset v2.7 APP Arina Puzriakova Classified gene: APP as Amber List (moderate evidence)
Leukodystrophy, adult onset v2.7 APP Arina Puzriakova Added comment: Comment on list classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotype (leukoencephalopathy) and age of onset (~44 to 60 years).
Leukodystrophy, adult onset v2.7 APP Arina Puzriakova Gene: app has been classified as Amber List (Moderate Evidence).
Leukodystrophy, adult onset v2.6 APP Arina Puzriakova Publications for gene: APP were set to
Leukodystrophy, adult onset v2.5 APP Arina Puzriakova Mode of inheritance for gene: APP was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Leukodystrophy, adult onset v2.4 APP Arina Puzriakova Phenotypes for gene: APP were changed from to Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants, OMIM:605714
Leukodystrophy, adult onset v2.3 APP Eleanor Williams reviewed gene: APP: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: CEREBRAL AMYLOID ANGIOPATHY,APP-RELATED; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Leukodystrophy, adult onset v2.2 APP Eleanor Williams gene: APP was added
gene: APP was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: APP was set to
Leukodystrophy, adult onset v1.38 LARS2 Sarah Leigh commented on gene: LARS2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Leukodystrophy, adult onset v1.25 EPRS Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber but with recommendation for green rating following GMS review. 4 unrelated cases. Presentation generally before age of 18 but after consultation with the Genomics England clinical team it was decided that it was also appropriate to propose as green on the adult onset panel.
Leukodystrophy, adult onset v1.14 CYP7B1 Arina Puzriakova Added comment: Comment on list classification: CYP7B1 will be flagged for GMS review to assess whether the phenotype is appropriate and there is enough potential clinical value to rate as Green on this panel.
Leukodystrophy, adult onset v0.22 KIF5A Louise Daugherty Added comment: Comment on list classification: Downgraded gene from Green to Amber from expert review David Lynch. This approach was also agreed in principle with the Genomic England clinical team (25th November 2019), the change will be flagged up in the sign-off email to the test group for this panel.
Leukodystrophy, adult onset v0.21 TYMP Louise Daugherty Added comment: Comment on list classification: Appropriate phenotype, sufficient cases, and external review all support gene-disease association.
Leukodystrophy, adult onset v0.20 SNORD118 Louise Daugherty Added comment: Comment on list classification: Appropriate phenotype, sufficient cases, and external review all support gene-disease association.
Leukodystrophy, adult onset v0.15 MARS Louise Daugherty commented on gene: MARS: Added new-gene-name tag, new approved HGNC gene symbol for MARS is MARS1
Leukodystrophy, adult onset v0.15 AARS Louise Daugherty commented on gene: AARS: Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1
Leukodystrophy, adult onset v0.15 DARS Louise Daugherty commented on gene: DARS: Added new-gene-name tag, new approved HGNC gene symbol for DARS is DARS1