Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes.
J Med Genet
; 41(10): 763-7, 2004 Oct.
Article
en En
| MEDLINE
| ID: mdl-15466010
ABSTRACT
BACKGROUND:
Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal recessive mode of inheritance and consists of at least three subtypes. FHL2 subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while FHL with MUNC13-4 mutation was recently identified and designated as FHL3 subtype.OBJECTIVE:
To examine MUNC13-4 mutations and the cytotoxic function of MUNC13-4 deficient T lymphocytes in Japanese FHL patientsMETHODS:
Mutations of MUNC13-4 and the cytotoxicity of MUNC13-4-deficient cytotoxic T lymphocytes (CTL) were analysed in 16 Japanese families with non-FHL2 subtype.RESULTS:
Five new mutations of the MUNC13-4 gene were identified in six families. The mutations were in the introns 4, 9, and 18, and exons 8 and 19. Two families had homozygous mutations, while the remaining four had compound heterozygous mutations. Cytotoxicity of MUNC13-4 deficient CTL was low compared with control CTL, but was still present. Clinically, the onset of disease tended to occur late; moreover, natural killer cell activity was not deficient in some FHL3 patients.CONCLUSIONS:
MUNC13-4 mutations play a role in the development of FHL3 through a defective cytotoxic pathway.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Histiocitosis de Células no Langerhans
/
Mutación
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Diagnostic_studies
Límite:
Female
/
Humans
/
Infant
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Med Genet
Año:
2004
Tipo del documento:
Article
País de afiliación:
Japón