A founder mutation in the MPL gene causes congenital amegakaryocytic thrombocytopenia (CAMT) in the Ashkenazi Jewish population.
Blood Cells Mol Dis
; 47(1): 79-83, 2011 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-21489838
ABSTRACT
Congenital amegakaryocytic thrombocytopenia (MIM #604498) (CAMT) is a rare inherited disease presenting as severe thrombocytopenia in infancy. Untreated, many CAMT patients develop aplastic anemia within the first decade of life; the only effective treatment of CAMT is bone marrow transplantation. CAMT is the result of the presence of homozygous or compound heterozygous mutations in the thrombopoietin receptor-encoding gene, MPL. We report here the identification and characterization of a founder mutation in MPL in the Ashkenazi Jewish (AJ) population. This mutation, termed c.79+2T>A, is a T to A transversion in the invariant second base of the intron 1 donor splice site. Analysis of a random sample of 2018 individuals of AJ descent revealed a carrier frequency of approximately 1 in 75. Genotyping of six loci adjacent to the MPL gene in the proband and in the 27 individuals identified as carriers of the c.79+2T>A mutation revealed that the presence of this mutation in the AJ population is due to a single founder. The observed carrier frequency predicts an incidence of CAMT in the AJ population of approximately 1 in 22,500 pregnancies. The identification of this mutation will enable population carrier testing and will facilitate the identification and treatment of individuals homozygous for this mutation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trombocitopenia
/
Efecto Fundador
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Receptores de Trombopoyetina
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Mutación
Tipo de estudio:
Etiology_studies
Límite:
Humans
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Male
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Newborn
Idioma:
En
Revista:
Blood Cells Mol Dis
Asunto de la revista:
HEMATOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos