Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state

Jdila, Marwa Ben; Issa, Abir Ben; Khabou, Boudour; Rhouma, Bochra Ben; Kamoun, Fatma; Keskes, Leila; Triki, Chahnez; Fakhfakh, Faiza

doi:10.1016/j.cca.2017.08.001

Cited by 11 publications

(19 citation statements)

References 33 publications

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“…Recently, both germline mosaicism and somatic mosaicism have also been reported as important mechanisms for early‐onset EE (Masliah‐Plachon et al, 2010). Examples of somatic mosaicism include KCNQ2 mutations in neonatal EE (Milh et al, 2015), CDKL5 mutations in West syndrome (Jdila et al, 2017; Kato et al, 2015; Masliah‐Plachon et al, 2010), paternal gonadal mosaicism of SCN1A mutations in Dravet syndrome (Depienne et al, 2010; Morimoto et al, 2006), and STXBP1 ‐related Ohtahara syndrome (Saitsu et al, 2010). Hence, through deep sequencing, we identified that 22.7% (5/22) of the “ de novo mutations in Sanger sequencing” are not really DNMs.…”

Section: Discussionmentioning

confidence: 99%

“…However, each gene is individually responsible for less than 1% of EE cases (Noebels, 2015; Ottman et al, 2010), implying complex genotypic heterogeneity of ISs. Besides the germline mutations, somatic mosaicism has recently emerged as an important cause of EE or ISs (Depienne et al, 2010; Jdila et al, 2017; Kato et al, 2015; Masliah‐Plachon et al, 2010; Milh et al, 2015; Saitsu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort

Liu

Wang

et al. 2021

Molec Gen & Gen Med

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort

Liu

Wang

et al. 2021

Molec Gen & Gen Med

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“…Genomic DNA was extracted from peripheral blood leukocytes using phenol– chloroform standard procedures (Lewin and Stewart‐Haynes, 1992; Jdila et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

A novel C‐terminal truncated mutation in hCDKL5 protein causing a severe West syndrome: Comparison with previous truncated mutations and genotype/phenotype correlation

Jdila

Triki

Rhouma

et al. 2018

Intl J of Devlp Neuroscience

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The impairment of alternative splicing of exon 19 and the lack of a part of the proteasome signal due to c.2788insG mutation could disrupt the dynamic regulation of isoform levels especially hCDKL5_5 and hCDKL5_1 during pre and postnatal neurodevelopment and then could cause pathogenic phenotype. Signal peptidase I serine active site seems to modulate hCDKL5_5 movements between nucleus and cytoplasm. We noticed that the resulting phenotypes from truncated mutations among the C-terminal domain of hCDKL5 are almost similar and are always severe.

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“…About 30% of TS patients present with IS (Saxena and Sampson, 2015). Of course, IS can occur in association with many disease states besides TS and FCD, including, but not limited to, lissencephaly (Herbst et al, 2016), Down syndrome (Daniels et al, 2019), mutations in the CDKL5 gene (Jdila et al, 2017), mutations of the STXBP1 gene (Li et al, 2018), and hypoxic-ischemic encephalopathy (Inoue et al, 2014). In this review, we attempt to illuminate the possible physiological mechanisms of epileptic spasms in general -mechanisms that may occur as a convergent pathology secondary to a range of primary identified pathologies.…”

Section: Introductionmentioning

confidence: 99%

Seizure initiation in infantile spasms vs. focal seizures: proposed common cellular mechanisms

Traub

Moeller

Rosch

et al. 2019

Reviews in the Neurosciences

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Infantile spasms (IS) and seizures with focal onset have different clinical expressions, even when electroencephalography (EEG) associated with IS has some degree of focality. Oddly, identical pathology (with, however, age-dependent expression) can lead to IS in one patient vs. focal seizures in another or even in the same, albeit older, patient. We therefore investigated whether the cellular mechanisms underlying seizure initiation are similar in the two instances: spasms vs. focal. We noted that in-common EEG features can include (i) a background of waves at alpha to delta frequencies; (ii) a period of flattening, lasting about a second or more – the electrodecrement (ED); and (iii) often an interval of very fast oscillations (VFO; ~70 Hz or faster) preceding, or at the beginning of, the ED. With IS, VFO temporally coincides with the motor spasm. What is different between the two conditions is this: with IS, the ED reverts to recurring slow waves, as occurring before the ED, whereas with focal seizures the ED instead evolves into an electrographic seizure, containing high-amplitude synchronized bursts, having superimposed VFO. We used in vitro data to help understand these patterns, as such data suggest cellular mechanisms for delta waves, for VFO, for seizure-related burst complexes containing VFO, and, more recently, for the ED. We propose a unifying mechanistic hypothesis – emphasizing the importance of brain pH – to explain the commonalities and differences of EEG signals in IS versus focal seizures.

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Novel mutations in the CDKL5 gene in complex genotypes associated with West syndrome with variable phenotype: First description of somatic mosaic state

Cited by 11 publications

References 33 publications

Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort

Confirming the contribution and genetic spectrum of de novo mutation in infantile spasms: Evidence from a Chinese cohort

A novel C‐terminal truncated mutation in hCDKL5 protein causing a severe West syndrome: Comparison with previous truncated mutations and genotype/phenotype correlation

Seizure initiation in infantile spasms vs. focal seizures: proposed common cellular mechanisms

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