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Optic neuropathy v5.47 BORCS5 Ida Ertmanska gene: BORCS5 was added
gene: BORCS5 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: BORCS5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BORCS5 were set to 27435318; 40385417; 40621786
Phenotypes for gene: BORCS5 were set to arthrogryposis multiplex congenita, MONDO:0015168; neurodevelopmental disorder, MONDO:0700092
Review for gene: BORCS5 was set to GREEN
Added comment: PMID: 40621786 Fisher et al., 2025
Report of 2 fetal cases in a consanguineous Pakistani family. Exome seq revealed a homozygous nonsense variant c.283C>T, p.(Arg95Ter) in BORCS5 (NM_058169.4). Individuals showed neuroaxonal dystrophy with osteopetrosis.

PMID: 40385417 Mencacci et al., 2025 - pre-print
Report of 12 individuals from 7 unrelated families with biallelic BORCS5 variants (NM_058169.4): two missense variants (c.284G>A, p.R95Q; c.296A>C, p.H99P) and four LoF alleles (c.203–1G>T, p.?; c.316delG, p.A106Pfs*20; c.382_383delAG, p.L128Vfs*86; c.417C>G, p.Y139*).
Table 1 = phenotypic spectrum of 6 individuals from families 1-4: profound ID (6/6), severe spasticity (6/6), seizures (6/6), hyperreflexia (6/6), Parkinsonism/dystonia (3/6), limb contractures (5/6), optic atrophy (5/6), abnormal brain MRI including cerebral atrophy and/or corpus callosum agenesis (5/6), microcephaly (6/6 - severity not stated), muscle atrophy (5/6). Infantile onset.
Neuroimaging in 5 cases showed cerebral atrophy, white matter loss, hypomyelination, small T2-hypointense thalami, thin brainstem, and optic nerve atrophy.

PMID: 27435318 Charng et al., 2016
Patient BAB6775 homozygous for NM_058169.4 BORCS5: c.203-1G>T, with DD, microcephaly, seizures, cortical malformations, polymicrogyria, agenesis of corpus callosum. Also reported with more details in PMID:40385417 (do not count).

Additional functional evidence: Zebrafish borcs5 knockout leads to neurodevelopmental defects:microcephaly, ventriculomegaly, movement disorders and epilepsy.

BORCS5 is not yet associated with a disease in OMIM (accessed 20th Feb 2026).
Sources: Literature
Optic neuropathy v4.40 MAG Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: MAG.
Optic neuropathy v4.40 MAG Achchuthan Shanmugasundram reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.39 MAG Achchuthan Shanmugasundram Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.11 MAG Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v3.18
Optic neuropathy v3.11 MAG Arina Puzriakova gene: MAG was added
gene: MAG was added to Optic neuropathy. Sources: Yorkshire and North East GLH,London North GLH,Literature,Expert Review Amber,NHS GMS
Q1_23_promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 24482476; 26179919; 31402626; 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680