Megalencephalic leukoencephalopathy with subcortical cysts type 1 (MLC1) due to a homozygous deep intronic splicing mutation (c.895-226T>G) abrogated in vitro using an antisense morpholino oligonucleotide.
Neurogenetics
; 13(3): 205-14, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22552818
ABSTRACT
Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive disease characterized by early onset macrocephaly; developmental delay; motor disability in the form of progressive spasticity and ataxia; seizures; cognitive decline; and characteristic magnetic resonance imaging findings. Mutations in two genes, MLC1 (22q13.33; 75 % of patients) or HEPACAM (11q24; 20 % of patients), are associated with the disease. We describe an adult MLC patient with moderate clinical symptoms. MLC1 cDNA analysis from lymphoblasts showed a strong transcript reduction and identified a 246-bp pseudoexon containing a premature stop codon between exons 10 and 11, due to a homozygous c.895-226 T>G deep-intronic mutation. This category of mutations is often overlooked, being outside of canonically sequenced genomic regions. The mutation c.895-226 T>G has a leaky effect on splicing leaving part of the full-length transcript. Its role on splicing was confirmed using a minigene assay and an antisense morpholinated oligonucleotide targeted to the aberrant splice site in vitro, which partially abrogated the mutation effect.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Íntrons
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Oligonucleotídeos Antissenso
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Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central
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Cistos
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Proteínas de Membrana
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Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article