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Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.

Fecha de publicación:

Autores de CIPF

  • María Dolores Martínez Rubio

    Autor

  • Mª Isabel Hinarejos Martinez

    Autor

  • Vincenzo Lupo

    Autor

Participantes ajenos a CIPF

  • Argente-Escrig H
  • Marco-Marín C
  • Lozano MA
  • Gorría-Redondo N
  • Martí-Carrera I
  • Miranda C
  • Vázquez-López M
  • García-Pérez A
  • Marco-Hernández AV
  • Tomás-Vila M
  • Aguilera-Albesa S

Grupos de Investigación

Abstract

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6 , CPLANE1 , and TBCD . The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.

Datos de la publicación

ISSN/ISSNe:
1422-0067, 1422-0067

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES  MDPI

Tipo:
Article
Páginas:
-
PubMed:
38003592

Citas Recibidas en Web of Science: 5

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Métricas

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Keywords

  • ataxia, cerebellar atrophy, exome sequencing, gene panel, neuroimaging, rare disease

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