Mutations in the X-linked Cyclin-dependent Kinase-like 5 (CDKL5/STK9) Gene Are Associated with Severe Neurodevelopmental Retardation

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2004 Oct 23

PMID 15499549

Citations 105

Authors

Jiong Tao

Hilde Van Esch

M Hagedorn-Greiwe

Kirsten Hoffmann

Bettina Moser

Martine Raynaud

Jurgen Sperner

Jean-Pierre Fryns

Eberhard Schwinger

Jozef Gecz

Hans-Hilger Ropers

Vera M Kalscheuer

Affiliations

Soon will be listed here.

Abstract

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. 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. The mutations are located within the protein kinase domain and affect highly conserved amino acids; this strongly suggests that impaired CDKL5 catalytic activity plays an important role in the pathogenesis of this neurodevelopmental disorder. In view of the overlapping phenotypic spectrum of CDKL5 and MECP2 mutations, it is tempting to speculate that these two genes play a role in a common pathogenic process.

Citing Articles

A Novel Mouse Model Unveils Protein Deficiency in Truncated CDKL5 Mutations.

Feng X, Zhu Z, Wang H, Zhou H, Liu J, Shen Y Neurosci Bull. 2025; .

PMID: 40042769 DOI: 10.1007/s12264-024-01346-4.

Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.

Song X, Xia Z, Martinez D, Xu B, Spritzer Z, Zhang Y Cell Rep Med. 2025; 6(2):101926.

PMID: 39855191 PMC: 11866500. DOI: 10.1016/j.xcrm.2024.101926.

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.

Bajikar S, Zhou J, OHara R, Tirumala H, Durham M, Trostle A Neuron. 2024; 113(3):380-395.e8.

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The genetic landscape of autism spectrum disorder in an ancestrally diverse cohort.

Gogate A, Kaur K, Khalil R, Bashtawi M, Morris M, Goodspeed K NPJ Genom Med. 2024; 9(1):62.

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Rett syndrome.

Gold W, Percy A, Neul J, Cobb S, Pozzo-Miller L, Issar J Nat Rev Dis Primers. 2024; 10(1):84.

PMID: 39511247 DOI: 10.1038/s41572-024-00568-0.

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