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| Lysosomal storage disorder v3.9 | CLCN7 |
Ida Ertmanska changed review comment from: PMID: 38838776 Polovitskaya et al., 2024 Report of unrelated male 2 individuals with hypopigmentation, muscular hypotonia, failure to thrive, organomegaly, delayed myelination, and psychomotor developmental disorder (no osteopetrosis), habrouring CLCN7 variants: p.Tyr715Cys (inheritance not confirmed) and p.Lys285Thr (de novo). PMID: 39056574 Lee et al., 2024 Report of a Taiwanese boy presenting with significant developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation (generalized hypopigmentation of the skin, hair, and ocular albinism that had been present since birth) without osteopetrosis. WES revealed a de novo GOF variant, p.Tyr715Cys in CLCN7.; to: PMID: 38838776 Polovitskaya et al., 2024 Report of unrelated male 2 individuals with hypopigmentation, muscular hypotonia, failure to thrive, organomegaly, delayed myelination, and psychomotor developmental disorder (no osteopetrosis), habrouring CLCN7 variants: p.Tyr715Cys (inheritance not confirmed) and p.Lys285Thr (de novo). Patient fibroblast studies showed that both disease-associated mutations affect the inhibition of ClC-7 by PI(3,5)P2 and shift its voltage-dependent gating to more physiological lysosomal voltages. PMID: 39056574 Lee et al., 2024 Report of a Taiwanese boy presenting with significant developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation (generalized hypopigmentation of the skin, hair, and ocular albinism that had been present since birth) without osteopetrosis. WES revealed a de novo GOF variant, p.Tyr715Cys in CLCN7. |
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| Lysosomal storage disorder v3.9 | CLCN7 | Ida Ertmanska commented on gene: CLCN7: Comment on list classification: There are now 5 unrelated individuals (4 male, 1 female) with Hypopigmentation, organomegaly, and delayed myelination and development, harbouring heterozygous CLCN7 variants. 4/5 patients had confirmed de novo status. 2 different variants were reported, with p.Tyr715Cys recurring in 4 unrelated patients. Based on available evidence, CLCN7 should be promoted to Green on Lysosomal storage disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v3.9 | CLCN7 |
Ida Ertmanska changed review comment from: PMID: 38838776 Polovitskaya et al., 2024 Report of 2 individuals with hypopigmentation, organomegaly, and delayed myelination and development (no osteopetrosis), habrouring CLCN7 variants: p.Tyr715Cys and novel p.Lys285Thr. PMID: 39056574 Lee et al., 2024 Report of a Taiwanese boy presenting with developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation without osteopetrosis. WES revealed a de novo GOF variant, p.Tyr715Cys in CLCN7.; to: PMID: 38838776 Polovitskaya et al., 2024 Report of unrelated male 2 individuals with hypopigmentation, muscular hypotonia, failure to thrive, organomegaly, delayed myelination, and psychomotor developmental disorder (no osteopetrosis), habrouring CLCN7 variants: p.Tyr715Cys (inheritance not confirmed) and p.Lys285Thr (de novo). PMID: 39056574 Lee et al., 2024 Report of a Taiwanese boy presenting with significant developmental delay, organomegaly, hypogammaglobulinemia and hypopigmentation (generalized hypopigmentation of the skin, hair, and ocular albinism that had been present since birth) without osteopetrosis. WES revealed a de novo GOF variant, p.Tyr715Cys in CLCN7. |
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| Lysosomal storage disorder v3.9 | CLCN7 | Ida Ertmanska Phenotypes for gene: CLCN7 were changed from Hypopigmentation, organomegaly, and delayed myelination and development, OMIM:618541 to Hypopigmentation, organomegaly, and delayed myelination and development, OMIM:618541; hypopigmentation, organomegaly, and delayed myelination and development, MONDO:0032805 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v3.8 | CLCN7 | Ida Ertmanska Publications for gene: CLCN7 were set to 31155284 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v3.7 | CLCN7 | Ida Ertmanska Mode of inheritance for gene: CLCN7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v3.6 | CLCN7 |
Ida Ertmanska Tag watchlist was removed from gene: CLCN7. Tag Q2_26_promote_green tag was added to gene: CLCN7. |
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| Lysosomal storage disorder v3.6 | CLCN7 | Ida Ertmanska reviewed gene: CLCN7: Rating: GREEN; Mode of pathogenicity: None; Publications: 38838776, 39056574; Phenotypes: Hypopigmentation, organomegaly, and delayed myelination and development, OMIM:618541; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v1.76 | CLCN7 | Arina Puzriakova Classified gene: CLCN7 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v1.76 | CLCN7 | Arina Puzriakova Added comment: Comment on list classification: Rating Amber as two individuals have been reported and with the same variant. Although there is some functional support, an additional independent case would help corroborate this association and indicate whether this is a variant specific phenotype. Different heterozygous CLCN7 variants have been linked to AD osteopetrosis. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v1.76 | CLCN7 | Arina Puzriakova Gene: clcn7 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Lysosomal storage disorder v1.75 | CLCN7 |
Arina Puzriakova gene: CLCN7 was added gene: CLCN7 was added to Lysosomal storage disorder. Sources: Literature watchlist tags were added to gene: CLCN7. Mode of inheritance for gene: CLCN7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CLCN7 were set to 31155284 Phenotypes for gene: CLCN7 were set to Hypopigmentation, organomegaly, and delayed myelination and development, OMIM:618541 Mode of pathogenicity for gene: CLCN7 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: CLCN7 was set to AMBER Added comment: Nicoli et al., 2019 (PMID: 31155284) reported on two unrelated individuals from different ethnic backgrounds with the same de novo gain-of-function missense variant (c.2144A>G, p.Tyr715Cys) in the CLCN7 gene. Both children had generalised cutaneous hypopigmentation without ocular involvement, delayed myelination and motor development, and organomegaly. Biopsies showed that both probands had cytoplasmic inclusions, characteristic of those seen in lysosomal-storage disorders. Human phenotypes were recapitulated by a mouse model harbouring the knock-in Clcn7 variant. This gene-disease relationship is listed in OMIM (MIM# 618541) but is not yet in G2P. Sources: Literature |
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