Regression
Gene: BORCS8
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, MIM# 620987
3 unrelated families with five affected children with homozygous or compound heterozygous loss of function missense and PTC variants. 5/5 hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy, dysmorphic features. 3/5 with microcephaly, 3/5 with seizures, 4/5 with spasticity, 3/5 with scoliosis, 4/4 with optic atrophy.
HEK293T cells show the missense variants are expressed at normal levels but exhibit reduced assembly with other BORC subunits and reduced ability to drive lysosome distribution. The BORCS8 PTC frameshift variant is expressed at lower levels and is completely incapable of assembling with other BORC subunits and promoting lysosome distribution. Zebrafish KO of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human disease.
Sources: LiteratureCreated: 4 Jan 2024, 1:42 a.m. | Last Modified: 4 Jan 2024, 1:51 a.m.
Panel Version: 0.540
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder (MONDO#0700092), BORCS8-related
Publications
Phenotypes for gene: BORCS8 were changed from Neurodevelopmental disorder (MONDO#0700092), BORCS8-related to Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, MIM# 620987
Gene: borcs8 has been classified as Green List (High Evidence).
Gene: borcs8 has been classified as Green List (High Evidence).
gene: BORCS8 was added gene: BORCS8 was added to Regression. Sources: Literature Mode of inheritance for gene: BORCS8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BORCS8 were set to 38128568 Phenotypes for gene: BORCS8 were set to Neurodevelopmental disorder (MONDO#0700092), BORCS8-related Review for gene: BORCS8 was set to GREEN