Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations.
J Intern Med
; 264(4): 388-400, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-18513342
ABSTRACT
OBJECTIVES:
Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms.METHODS:
Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues.RESULTS:
Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C-->T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G-->A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5' end of exon 2 containing the W44X mutation was spliced out from the second transcript.CONCLUSIONS:
We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas
/
Doenças do Sistema Nervoso Central
/
Neutropenia
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Intern Med
Assunto da revista:
MEDICINA INTERNA
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Suécia