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Homozygous variant of MLC1 results in megalencephalic leukoencephalopathy with subcortical cysts.
Zha, Jian; Chen, Yong; Cao, Fangfang; Xu, Yuxin; Yang, Zuozhen; Wen, Shu; Liang, Mengmeng; Wu, Huaping; Zhong, Jianmin.
Afiliação
  • Zha J; Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
  • Chen Y; Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
  • Cao F; Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
  • Xu Y; Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
  • Yang Z; Cipher Gene LLC, Beijing, China.
  • Wen S; Cipher Gene LLC, Beijing, China.
  • Liang M; Cipher Gene LLC, Beijing, China.
  • Wu H; Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
  • Zhong J; Department of Neurology, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi, China.
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central / Cistos / Megalencefalia Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central / Cistos / Megalencefalia Idioma: En Ano de publicação: 2024 Tipo de documento: Article