Hereditary Neuropathy - complex

Gene: MCM3AP

Green List (high evidence)

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: 1 Jul 2020, 7:27 a.m. | Last Modified: 1 Jul 2020, 7:27 a.m.

Panel Version: 0.64

At least 10 families reported.
Sources: Expert list

Created: 7 Mar 2020, 6:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development, MIM#618124

Publications

• 24123876
• 28633435
• 28969388
• 29982295
• 32202298

Variants in this GENE are reported as part of current diagnostic practice