White matter disorders and cerebral calcification - narrow panel
Gene: MAL
Not associated with a phenotype in OMIM, Gen2Phen or MONDO. One variant (c.326C>A, p.Ala109Asp) has been reported in a consanguineous family with rare, hypomyelinating leukodystrophy similar to Pelizaeus-Merzbacher disease (PMID: 35217805). Functional studies in PMID: 35217805 suggest that the variant results in mislocalisation of MAL, affecting proteolipid protein 1 (PLP1) distribution. PLP1 has previously been associated with Pelizaeus-Merzbacher disease.Created: 12 Jul 2022, 1:28 p.m. | Last Modified: 12 Jul 2022, 1:28 p.m.
Panel Version: 1.159
Single consanguineous family reported with two affected children (DD and nystagmus). New onset ataxia and cerebellar volume loss with patchy dysmyelination. Homozygous missense variant identified by exome analysis segregated with the condition. Functional data suggested that p.(Ala109Asp) severely affects protein folding of MAL, leading to mislocalization in the ER.
Sources: LiteratureCreated: 11 Jul 2022, 11:56 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
developmental delay; nystagmus; progressive motor deterioration; dysmyelination
Publications
gene: MAL was added gene: MAL was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MAL were set to 35217805 Phenotypes for gene: MAL were set to developmental delay; nystagmus; progressive motor deterioration; dysmyelination