Childhood onset hereditary spastic paraplegia
Gene: BCAS3The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.Created: 14 Mar 2022, 1:30 p.m. | Last Modified: 14 Mar 2022, 1:30 p.m.
Panel Version: 2.130
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update (see details below).
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Hengel et al. 2021 (PMID: 34022130) report 8 unrelated families, all with different biallelic variants in the BCAS3 gene. All affected individuals (15 total, +1 additional proband but with unphased variants but consistent phenotype) had severe GDD and ID, with 10 subjects having minimal vocabulary and 4 never learning to speak. All probands had a severe motor disorder with pyramidal tract involvement resulting in hyperreflexia and spasticity of the lower limbs (15/15). Other variable features observed in the cohort include microcephaly, short stature, seizures, and dysmorphic facial features.Created: 23 Jun 2021, 10:26 a.m. | Last Modified: 23 Jun 2021, 10:26 a.m.
Panel Version: 3.1143
15 individuals from eight unrelated families with germline bi-allelic loss-of-function variants in BCAS3. All probands share a global developmental delay accompanied by pyramidal tract involvement, microcephaly, short stature, strabismus, dysmorphic facial features, and seizures. Patient fibroblasts confirmed absence of BCAS3 protein.
Sources: LiteratureCreated: 11 Jun 2021, 10:48 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Syndromic neurodevelopmental disorder
Publications
Tag Q2_21_rating was removed from gene: BCAS3.
Source Expert Review Green was added to BCAS3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
gene: BCAS3 was added gene: BCAS3 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature Q2_21_rating tags were added to gene: BCAS3. Mode of inheritance for gene: BCAS3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BCAS3 were set to 34022130 Phenotypes for gene: BCAS3 were set to Syndromic neurodevelopmental disorder