Molecular analysis of immunized Jr(a-) or Lan- patients and validation of a high-throughput genotyping assay to screen blood donors for Jr(a-) and Lan- phenotypes.
Transfusion
; 54(7): 1836-46, 2014 Jul.
Article
en En
| MEDLINE
| ID: mdl-24456066
ABSTRACT
BACKGROUND:
Individuals with anti-Jr(a) or anti-Lan are ideally transfused with rare Jr(a-) or Lan- red blood cells. We characterized mutations in Dutch Jr(a-) and Lan- individuals and developed a high-throughput genotyping assay to detect Jr(a-) and Lan- donors. STUDY DESIGN ANDMETHODS:
Six Jr(a-) and seven Lan- persons, who all made anti-Jr(a) or anti-Lan, were sequenced for ABCG2 or ABCB6 and the copy number of ABCG2 and ABCB6 was determined. A total of 3366 Caucasian, 621 black, and 333 Chinese donors were screened with a high-throughput screening assay targeting frequently occurring mutations causing the Jr(a-) or Lan- phenotype.RESULTS:
In the six tested Jr(a-) individuals previously described, c.376C > T, c.706C > T, and c.736C > T nonsense mutations in ABCG2 were detected. In the seven Lan- individuals 12 different mutations, of which 10 underlie the Lan- phenotype, were detected. No copy number variation was detected for ABCG2 and ABCB6. The high-throughput screening assay detected five Caucasian donors heterozygous for the c.706C > T or 736C > T mutation in ABCG2 and nine Caucasian donors heterozygous for the 574C > T mutation in ABCB6. No black or Chinese donors were found positive for a mutation.CONCLUSION:
We describe eight new mutations in ABCB6 of which seven, including three missense mutations, underlie the Lan- phenotype and determine that a complete gene deletion of ABCG2 or ABCB6 is not responsible for the Jr(a-) or Lan- phenotype, respectively. The extended heterogeneity of mutations causing the Jr(a-) or Lan- phenotype in most populations makes genetic screening for the Jr(a-) and Lan- phenotype inefficient in those populations.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Donantes de Sangre
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Antígenos de Grupos Sanguíneos
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Análisis de Secuencia de ADN
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Ensayos Analíticos de Alto Rendimiento
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Técnicas de Genotipaje
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Isoantígenos
Límite:
Humans
País/Región como asunto:
Africa
/
Europa
Idioma:
En
Revista:
Transfusion
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos