Disease relevance of CDKL5

• Mutations of CDKL5 cause a severe neurodevelopmental disorder with infantile spasms and mental retardation [1].
• These findings confirm CDKL5 as another locus associated with epilepsy and X-linked mental retardation [1].
• Moreover, this report reinforces the observation that the CDKL5 phenotype overlaps with Rett syndrome and that CDKL5 gene analysis is recommended in females with a seizure disorder commencing in the first weeks of life [2].
• Myoclonic encephalopathy in the CDKL5 gene mutation [3].

Psychiatry related information on CDKL5

• Patients with CDKL5 mutations sometimes also show features similar to those seen in Rett Syndrome (RTT) [4].

High impact information on CDKL5

• These results also suggest that mutations in CDKL5 can lead to a clinical phenotype that overlaps RTT [1].
• The ARX and CDKL5 genes, both of which are located within the Xp22 region, were sequenced in the affected family members, and a deletion of nucleotide 183 of the coding sequence (c.183delT) was identified in CDKL5 in the affected family members [1].
• Recently, we showed that truncation of the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene caused mental retardation and severe neurological symptoms in two female patients [5].
• We show that STK9 is subject to X-inactivation in normal female somatic cells and is functionally absent in the two patients, because of preferential inactivation of the normal X [6].
• Furthermore, this paper contributes to the clarification of the phenotype associated with CDKL5 mutations and indicates that CDKL5 should be analyzed in each patient showing a clinical course similar to RTT but characterized by a lack of an early normal period due to the presence of seizures [7].

Biological context of CDKL5

• Here, we report that de novo missense mutations in CDKL5 are associated with a severe phenotype of early-onset infantile spasms and clinical features that overlap those of other neurodevelopmental disorders, such as Rett syndrome and Angelman syndrome [5].
• Furthermore, we show that CDKL5 can self-associate and mediate the phosphorylation of its own TEY (Thr-Glu-Tyr) motif [8].
• Functional Consequences of Mutations in CDKL5, an X-linked Gene Involved in Infantile Spasms and Mental Retardation [8].
• Sequence homologies, expression pattern, and mapping information in both human and mouse make STK9 a candidate gene for the above-mentioned disorders [9].

Other interactions of CDKL5

• Mutation analysis of the HDAC 1, 2, 8 and CDKL5 genes in Rett syndrome patients without mutations in MECP2 [10].
• OBJECTIVE: Epilepsy with mutation of the CDKL5 gene causes early seizures and is a variant of Rett syndrome (MIM (312750), which is reported typically as infantile spasms [3].
• Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes [11].

Analytical, diagnostic and therapeutic context of CDKL5

• CONCLUSIONS: Patients with the CDKL5 mutation have an early onset, epileptic encephalopathy in infancy that evolves into myoclonic seizures in childhood with a unique EEG pattern [3].
• The remaining cases without MECP2 mutations were screened for the cyclin-dependent kinase-like 5 (CDKL5) gene using denaturing high-performance liquid chromatography (DHPLC) [12].

References