Hereditary neuropathy NOT PMP22 copy numberGene: 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, 4:27 p.m. | Last Modified: 30 Jun 2020, 4:27 p.m.
Panel Version: 1.4
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.
Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) New evidence/re-evaluation of evidence - promotion to Green/ New evidence - PMID:28633435
Created: 6 Dec 2019, 2:33 p.m. | Last Modified: 6 Dec 2019, 2:33 p.m.
Panel Version: 0.36
Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) 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, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.
Created: 6 Dec 2019, 1:20 p.m. | Last Modified: 6 Dec 2019, 1:20 p.m.
Panel Version: 0.14
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 28633435
Publications for gene: MCM3AP were set to
Gene: mcm3ap has been classified as Green List (High Evidence).
gene: MCM3AP was added gene: MCM3AP was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, 618124