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| Bleeding and Platelet Disorders v1.27 | APOLD1 |
Lucy Spencer changed review comment from: PMID: 35638551 1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant. This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis. Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. Sources: Literature; to: PMID: 35638551 1 family with an atypical inherited bleeding disorder characterised by severe spontaneous bleeding episodes in childhood and microcirculatory problems. 4 affected individuals across 2 generations have R49*in APOLD1, another affected individual from a third generation was not able to be sequenced = 4 meiosis. 4 unaffected individuals did not have the variant. This gene has no NMD region, R49* would affect 82% of the protein. Paper is not using the MANE select transcript, alt p. in MANE select is R18* which affects 92% of the MANE select protein Interestingly R49* is created by a delins/2 missense in cis, 1 common R49Q and 1 rare R49W, some UNaffected family members just have the common missense without the other in cis. Immunofluorescence studies in patient platelets showed a 50% reduction of APOLD1 and disrupted cytoskeletal and junctional organization. SiRNA silencing of APOLD1 in HBDEC cells resulted in altered cell shape and size, and were associated with endothelial cell junction dismantling. These cells were also almost devoid of VWF. Sources: Literature |
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| Bleeding and Platelet Disorders v0.2 | VWF | Zornitza Stark Marked gene: VWF as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.2 | VWF | Zornitza Stark Gene: vwf has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.2 | VWF | Zornitza Stark Phenotypes for gene: VWF were changed from to von Willebrand disease, type 1, MIM#193400; von Willebrand disease, types 2A, 2B, 2M, and 2N, MIM#613554; von Willibrand disease, type 3, MIM#277480 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.1 | VWF | Zornitza Stark Mode of inheritance for gene: VWF was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.0 | VWF |
Chern Lim changed review comment from: Loss of function variants have been reported in both dominant and recessive form of disease (PMID:12588351 , PMID:16643449). VWD type 3 (AR) usually carries null alleles, VWD type 1 (AD) is usually due to partial deficiency (PMID:19372260). Dominant negative have been reported for missense variant (PMID:11698279).; to: Loss of function variants have been reported in both dominant and recessive forms of disease (PMID:12588351 , PMID:16643449). VWD type 3 (AR) usually associated with null alleles, VWD type 1 (AD) is usually due to partial deficiency (PMID:19372260). Dominant negative have been reported for missense variant (PMID:11698279). |
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| Bleeding and Platelet Disorders v0.0 | VWF | Chern Lim reviewed gene: VWF: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: von Willebrand disease, type 1, MIM#193400, von Willebrand disease, types 2A, 2B, 2M, and 2N, MIM#613554, von Willibrand disease, type 3, MIM#277480; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Bleeding and Platelet Disorders v0.0 | VWF |
Zornitza Stark gene: VWF was added gene: VWF was added to Bleeding Disorders_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: VWF was set to Unknown |
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