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Hereditary neuropathy or pain disorder v6.148 NDUFS6 Sarah Leigh Tag Q3_24_promote_green was removed from gene: NDUFS6.
Tag Q3_24_NHS_review was removed from gene: NDUFS6.
Hereditary neuropathy or pain disorder v6.148 NDUFS6 Sarah Leigh reviewed gene: NDUFS6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.147 NDUFS6 Sarah Leigh Source NHS GMS was added to NDUFS6.
Source Expert Review Green was added to NDUFS6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v6.16 NDUFS6 Eleanor Williams Publications for gene: NDUFS6 were set to 38459834; 38549004
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: NDUFS6.
Tag Q3_24_NHS_review tag was added to gene: NDUFS6.
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Classified gene: NDUFS6 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a recommendation for green rating following GMS review. 3 separate publications report variants in this gene in patients with peripheral neuropathies. 2 different variants are reported.
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Gene: ndufs6 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams changed review comment from: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 and PubMed: 15372108).

There is now phenotypic expansion with 4 families reported with a less severe phenotype. 3 families share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.; to: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 Spiegal et al 2009 and PubMed: 15372108 Kirby et al 2004, PMID: 30948790 - Rouzier et al 2019, PMID: 22474353 Ke et al 2012).

There is now phenotypic expansion with 5 families reported with a less severe phenotype. 4 families share a common variant.

PMID: 38459834 - Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.

PMID: 38217609 - Gangfuß et al 2024 - identified a homozygous variant (c.309 + 5 G > A) in NDUFS6 in one male patient aged 10 with axonal neuropathy accompanied by loss of small fibers in skin biopsy. The patient also showed optic atrophy and borderline intellectual disability.
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams changed review comment from: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome. 4 families reported although 3 share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.; to: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 and PubMed: 15372108).

There is now phenotypic expansion with 4 families reported with a less severe phenotype. 3 families share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams Phenotypes for gene: NDUFS6 were changed from Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232; mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615 to Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232; mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615
Hereditary neuropathy or pain disorder v6.13 NDUFS6 Eleanor Williams Phenotypes for gene: NDUFS6 were changed from peripheral neuropathy; nystagmus to Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232; mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615
Hereditary neuropathy or pain disorder v6.12 NDUFS6 Eleanor Williams Publications for gene: NDUFS6 were set to 38459834 : 38549004
Hereditary neuropathy or pain disorder v6.11 NDUFS6 Eleanor Williams edited their review of gene: NDUFS6: Changed publications to: 38459834, 38549004; Changed phenotypes to: Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232, mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.11 NDUFS6 Eleanor Williams commented on gene: NDUFS6
Hereditary neuropathy or pain disorder v5.19 NDUFS6 Alexander Rossor gene: NDUFS6 was added
gene: NDUFS6 was added to Hereditary neuropathy or pain disorder. Sources: Expert list
Mode of inheritance for gene: NDUFS6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFS6 were set to 38459834 : 38549004
Phenotypes for gene: NDUFS6 were set to peripheral neuropathy; nystagmus
Penetrance for gene: NDUFS6 were set to Complete
Review for gene: NDUFS6 was set to GREEN
Added comment: Sources: Expert list