Hereditary neuropathyGene: MCM3AP
PMID: 32202298 - Woldegebriel et al 2020 - report a further two families, one in the Netherlands and one in Estonia, with probands with compound heterozygous variants in MCM3AP and a peripheral neuropathy with or without impaired intellectual development (MIM 618124) phenotype. The child from the Netherlands presented with severe hypotonia and intellectual disability. The two siblings from the Estonian family had severe generalized epilepsy and mild spastic diplegia. Functional studies using skin fibroblasts from these and other affected patients showed that disease variants result in depletion of GANP (encoded by MCM3AP) except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants.
Created: 30 Jun 2020, 4:07 p.m. | Last Modified: 30 Jun 2020, 4:07 p.m.
Panel Version: 1.368
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
peripheral neuropathy with or without impaired intellectual development, 618124
Now reported in multiple CMT2 families with complex phenotype
Created: 9 May 2019, 12:20 p.m.
The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.
Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.
Panel Version: 1.352
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 5 p.m.
Publications for gene: MCM3AP were set to
Source Expert Review Green was added to MCM3AP. Rating Changed from Red List (low evidence) to Green List (high evidence)
Mode of inheritance for gene: MCM3AP was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MCM3AP were changed from to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, 618124
Source NHS GMS was added to MCM3AP.
gene: MCM3AP was added gene: MCM3AP was added to Hereditary neuropathy. Sources: London North GLH Mode of inheritance for gene: MCM3AP was set to