Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness.
Nat Genet
; 41(1): 106-11, 2009 Jan.
Article
en En
| MEDLINE
| ID: mdl-19043416
ABSTRACT
Reticular dysgenesis is an autosomal recessive form of human severe combined immunodeficiency characterized by an early differentiation arrest in the myeloid lineage and impaired lymphoid maturation. In addition, affected newborns have bilateral sensorineural deafness. Here we identify biallelic mutations in AK2 (adenylate kinase 2) in seven individuals affected with reticular dysgenesis. These mutations result in absent or strongly decreased protein expression. We then demonstrate that restoration of AK2 expression in the bone marrow cells of individuals with reticular dysgenesis overcomes the neutrophil differentiation arrest, underlining its specific requirement in the development of a restricted set of hematopoietic lineages. Last, we establish that AK2 is specifically expressed in the stria vascularis region of the inner ear, which provides an explanation of the sensorineural deafness in these individuals. These results identify a previously unknown mechanism involved in regulation of hematopoietic cell differentiation and in one of the most severe human immunodeficiency syndromes.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenilato Quinasa
/
Pérdida Auditiva Sensorineural
/
Sistema Hematopoyético
/
Isoenzimas
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
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Male
/
Newborn
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Francia