| Autor: |
Máté, A., Szakszon, K., Nagy, A.J., Zombor, M., Rudas, G., Zimmermann, A., van Ruissen, F., Baas, F., Sztriha, L. |
| Zdroj: |
European Journal of Paediatric Neurology; May2015 Supplement 1, Vol. 19, pS124-S124, 1p |
| Abstrakt: |
Objective The CASK protein is a member of the membraneassociated guanylate kinase protein family, and plays a role in neural development and synaptic function. The CASK gene is located on the X-chromosome, its loss-of-function mutations have been shown to cause microcephaly and pontine and cerebellar hypoplasia (MIC-PCH) in females. We report the cases of two girls with MIC-PCH caused by different de novo loss-of function mutations of the CASK gene. Methods Clinical evaluation included neurological examination, developmental assessment, brain MRI, EEG, laboratory tests, audiologic and ophthalmologic examinations, and genetic testing. Sequence analysis of the entire coding region (exons 1–27), and all intron-exon boundaries of the CASK gene was carried out. Results Both patients presented with congenital microcephaly, intellectual disability, delayed motor development in association with therapy-resistant epilepsy beginning around 2 years of age. Brain MRI revealed hypoplasia of the brainstem and cerebellum and the EEG showed bilateral periodic spike-and-wave discharges in both girls. One of them had a very severe phenotype with spastic tetraplegia, visual impairment and hearing loss, while the other patient was able to achieve some motor milestones like rolling and sitting with support. Pathogenic heterozygous deletions in the CASK gene were identified in both girls: deletion of 8 nucleotides (c.20_27delTGTTCGAG p.Leu7ArgfsX35) in one of them and deletion of a single nucleotide (c.1034delG p.Arg345Lysfs*) in the other one. Both deletions result in a frameshift leading to the formation of a premature stop codon. The parents are healthy. Conclusion Mutations of the CASK gene should be considered in female patients with microcephaly, intellectual disability and pontocerebellar hypoplasia. These girls are sporadic cases with de novo mutations. Identification of CASK mutations enables accurate and reassuring genetic counselling. [ABSTRACT FROM AUTHOR] |
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