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| Adult onset leukodystrophy v1.47 | TPP2 | Eleanor Williams Phenotypes for gene: TPP2 were changed from White matter abnormalities; autoimmunity; immunodefficiency; developmental delay to White matter abnormalities; Immunodeficiency 78 with autoimmunity and developmental delay, OMIM:619220 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.46 | TPP2 |
Eleanor Williams changed review comment from: Associated with Immunodeficiency 78 with autoimmunity and developmental delay, #619220 in OMIM. 2 cases reported of homozygous missense variants in TPP2 and a MS-type phenotype. However, 1 of the variants is also found in some MS patients in the heterozygous state. PMID: 33586135 - Atallah et al 2021- (not PMID: 25414442) summarises 14 patients with TPP2 pathogenic variants reported in their study and other publications. They report that 'the adult form, described in four patients, manifests as a chronic non-infectious brain inflammation with demyelinating brain disease and calcifications somewhat similar to multiple sclerosis.'. These 4 patients are reported in PMID: 30533531 (Reinthaler et al 2018) who describe a Syrian family with milder symptoms of sterile brain inflammation mimicking MS and no developmental delay. A missense variant, c.82T>G, p.Cys28Gly, in TPP2 was identified in all 3 affected siblings of the family. A Jordian patient with MS was also identified to have a homozygous missense variant (c.2027C>T, p.Thr676Ile) in TPP2. This variant also occurs in heterozygous form in other MS cases and in 6 ExAC control individuals so the authors acknowledge that it may not be pathogenic.; to: Associated with Immunodeficiency 78 with autoimmunity and developmental delay, #619220 in OMIM. 2 cases reported of homozygous missense variants in TPP2 and a MS-type phenotype. However, 1 of the variants is also found in some MS patients in the heterozygous state. PMID: 33586135 - Atallah et al 2021- (not PMID: 25414442) summarises 14 patients with TPP2 pathogenic variants reported in their study and other publications. They report that 'the adult form, described in four patients, manifests as a chronic non-infectious brain inflammation with demyelinating brain disease and calcifications somewhat similar to multiple sclerosis.'. These 4 patients are reported in PMID: 30533531 (Reinthaler et al 2018) who describe a Syrian family with milder symptoms of sterile brain inflammation mimicking MS and no developmental delay. A missense variant, c.82T>G, p.Cys28Gly, in TPP2 was identified in all 3 affected siblings of the family. A Jordian patient with MS was also identified to have a homozygous missense variant (c.2027C>T, p.Thr676Ile) in TPP2. This variant also occurs in heterozygous form in other MS cases and in 6 ExAC control individuals so the authors acknowledge that it may not be pathogenic. Age of diagnosis for these patients was 35 year plus. Other cases with variants in this gene are reported in PMIDS: 25414442; 25525876; 30533531, however these present in childhood with a recurrent respiratory infections, autoimmune cytopenias, developmental delay and progressive combined immunodeficiency. |
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| Adult onset leukodystrophy v1.46 | TPP2 | Eleanor Williams Publications for gene: TPP2 were set to 33586135 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.45 | TPP2 | Eleanor Williams Publications for gene: TPP2 were set to PMID:25414442 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.44 | TPP2 | Eleanor Williams Classified gene: TPP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.44 | TPP2 | Eleanor Williams Added comment: Comment on list classification: Promoting from grey to amber. 2 cases (4 individuals) with homozygous variants in this gene reported with an MS-like phenotype, but some doubt over the pathogenicity of the variant in 1 case. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.44 | TPP2 | Eleanor Williams Gene: tpp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.43 | TPP2 | Eleanor Williams reviewed gene: TPP2: Rating: ; Mode of pathogenicity: None; Publications: 33586135, 25414442, 25525876, 30533531; Phenotypes: ; Mode of inheritance: None | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.36 | TPP2 | Dmitrijs Rots edited their review of gene: TPP2: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adult onset leukodystrophy v1.36 | TPP2 |
Dmitrijs Rots changed review comment from: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis. Sources: Literature; to: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis. Should be rated green. Sources: Literature |
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| Adult onset leukodystrophy v1.36 | TPP2 |
Dmitrijs Rots changed review comment from: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis. Sources: Literature; to: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis. Sources: Literature |
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| Adult onset leukodystrophy v1.36 | TPP2 |
Dmitrijs Rots gene: TPP2 was added gene: TPP2 was added to White matter disorders - adult onset. Sources: Literature Mode of inheritance for gene: TPP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TPP2 were set to PMID:25414442 Phenotypes for gene: TPP2 were set to White matter abnormalities; autoimmunity; immunodefficiency; developmental delay Added comment: 14 individuals with "TRIANGLE" (TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion) syndrome are summarized in 25414442, where 4/14 presented in adulthood with white matter leasions mimicking multiple sclerosis. Sources: Literature |
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