Homozygous variant of MLC1 results in megalencephalic leukoencephalopathy with subcortical cysts.
Mol Genet Genomic Med
; 12(2): e2394, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38337154
ABSTRACT
BACKGROUND:
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited disorder that causes epilepsy, intellectual disorders, and early onset macrocephaly. MLC1 has been identified as a main pathogenic gene.METHODS:
Clinical data such as magnetic resonance imaging (MRI), routine blood tests, and physical examinations were collected from proband. Trio whole-exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (<0.01) in the exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated using Sanger sequencing.RESULTS:
Here, we report a new homozygous variant identified in two children from the same family in the MLC1 gene [NM_015166.4 c.838_843delinsATTTTA, (p.Ser280_Phe281delinsIleLeu)]. This variant is classified as variant of uncertain significance (VUS) according to the ACMG guidelines. Further experiments demonstrate that the newly identified variant causes a decrease of MLC1 protein levels when expressed in a heterologous expression system.CONCLUSION:
Our case expands on this genetic variation and provides new evidence for the clinical diagnosis of MLC1-related MLC.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central
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Cistos
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Megalencefalia
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article