Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novo PTEN mutation.
Neurology
; 90(21): e1842-e1848, 2018 05 22.
Article
em En
| MEDLINE
| ID: mdl-29720545
ABSTRACT
OBJECTIVE:
To describe a patient with a multifocal demyelinating motor neuropathy with onset in childhood and a mutation in phosphatase and tensin homolog (PTEN), a tumor suppressor gene associated with inherited tumor susceptibility conditions, macrocephaly, autism, ataxia, tremor, and epilepsy. Functional implications of this protein have been investigated in Parkinson and Alzheimer diseases.METHODS:
We performed whole-exome sequencing in the patient's genomic DNA validated by Sanger sequencing. Immunoblotting, in vitro enzymatic assay, and label-free shotgun proteomic profiling were performed in the patient's fibroblasts.RESULTS:
The predominant clinical presentation of the patient was a childhood onset, asymmetric progressive multifocal motor neuropathy. In addition, he presented with macrocephaly, autism spectrum disorder, and skin hamartomas, considered as clinical criteria for PTEN-related hamartoma tumor syndrome. Extensive tumor screening did not detect any malignancies. We detected a novel de novo heterozygous c.269T>C, p.(Phe90Ser) PTEN variant, which was absent in both parents. The pathogenicity of the variant is supported by altered expression of several PTEN-associated proteins involved in tumorigenesis. Moreover, fibroblasts showed a defect in catalytic activity of PTEN against the secondary substrate, phosphatidylinositol 3,4-trisphosphate. In support of our findings, focal hypermyelination leading to peripheral neuropathy has been reported in PTEN-deficient mice.CONCLUSION:
We describe a novel phenotype, PTEN-associated multifocal demyelinating motor neuropathy with a skin hamartoma syndrome. A similar mechanism may potentially underlie other forms of Charcot-Marie-Tooth disease with involvement of the phosphatidylinositol pathway.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neuropatia Hereditária Motora e Sensorial
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Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central
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PTEN Fosfo-Hidrolase
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Hamartoma
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Revista:
Neurology
Ano de publicação:
2018
Tipo de documento:
Article