Intellectual disability update Jan 2018

Gene: GBA2

Comment when marking as ready: Phenotype not a clear fit for this panel on the current evidence.

Created: 6 Mar 2018, 4:52 p.m.

Comment on list classification: I recognise that there are cases with intellectual impairment reported, however all cases reported to date have initially presented with gait disturbance or spasticity in the 1st-2nd decades. Therefore on the current evidence, the best place to capture phenotypes associated with this gene would be the HSP panel. If evidence emerges of a primary ID phenotype (rather than more complex neurological decline) then this can be re-considered.

Created: 6 Mar 2018, 4:51 p.m.

Comment on list classification: I recognise that there are cases with intellectual impairment reported, however all cases reported to date have initially presented with gait disturbance or spasticity in the 1st-2nd decades. Therefore on the current evidence, the best place to capture phenotypes associated with this gene would be the HSP panel. If evidence emerges of a primary ID phenotype (rather than more complex neurological decline) then this can be re-considered.

Created: 6 Mar 2018, 4:51 p.m.

Comment on phenotypes: Mild to moderate mental retardation reported in some patients and overall cognitive decline generally reported according PMID 23332916

Created: 5 Mar 2018, 11:43 a.m.

Comment when marking as ready: Spastic paraplegia 46, autosomal recessive 614409

Created: 5 Mar 2018, 11:40 a.m.

Associated with phenotype in OMIM and as a confirmed G2P association for Spastic paraplegia 46, autosomal recessive 614409, however, intellectual disability is not a common feature of this phenotype.
Based on report of a variant in two unrelated cases of Marinesco-Sjögren-Like Syndrome (PMID 28052128) in addition to at least three cases of Spastic paraplegia 46, autosomal recessive 614409 that display intellectual disability (PMIDs 23332916;23332917;24252062)

Created: 5 Mar 2018, 11:17 a.m.