De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus.
Neuron
; 99(2): 302-314.e4, 2018 07 25.
Article
en En
| MEDLINE
| ID: mdl-29983323
ABSTRACT
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations TRIM71 (p = 2.15 × 10-7), SMARCC1 (p = 8.15 × 10-10), and PTCH1 (p = 1.06 × 10-6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10-4). Together, these probands account for â¼10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células-Madre Neurales
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Hidrocefalia
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Mutación
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos