A novel mutation in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene associated with a severe Rett phenotype.
Am J Med Genet A
; 149A(4): 722-5, 2009 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-19253388
ABSTRACT
Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have recently been reported in patients with severe neurodevelopmental disorder characterized by early-onset seizures, infantile spasms, severe psychomotor impairment and very recently, in patients with Rett syndrome (RTT)-like phenotype. Although the involvement of CDKL5 in specific biological pathways and its neurodevelopmental role have not been completely elucidated, the CDKL5 appears to be physiologically related to the MECP2 gene. Here we report on the clinical and CDKL5 molecular investigation in a very unusual RTT case, with severe, early-neurological involvement in which we have shown in a previous report, a novel P388S MECP2 mutation [Conforti et al. (2003); Am J Med Genet A 117A 184-187]. The patient has had severe psychomotor delay since the first month of life and infantile spasms since age 5 months. Moreover, at age 5 years the patient suddenly presented with renal failure. The severe pattern of symptoms in our patient, similar to a CDKL5 phenotype, prompted us to perform an analysis of the CDKL5, which revealed a novel missense mutation never previously described. The X-inactivation assay was non-informative. In conclusion, this report reinforces the observation that the CDKL5 phenotype overlaps with RTT and that CDKL5 analysis is recommended in patients with a seizure disorder commencing during the first months of life.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Rett
/
Proteínas Serina-Treonina Quinases
/
Mutação de Sentido Incorreto
Tipo de estudo:
Risk_factors_studies
Limite:
Adolescent
/
Female
/
Humans
Idioma:
En
Revista:
Am J Med Genet A
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Itália