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Eur J Haematol. 2018 Oct;101(4):496-501. doi: 10.1111/ejh.13133. Epub 2018 Aug 3.

SMYD1 is the underlying gene for the AnWj-negative blood group phenotype.

Author information

1
Magen David Adom (MDA) National Blood Services, Tel Hashomer, Ramat Gan, Israel.
2
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
3
School of Medicine, Health Science Centre, Shenzhen University, Shenzhen, China.
4
BGI-Shenzhen, Shenzhen, China.
5
The Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
6
The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.
7
The Amalia Biron Research Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel.

Abstract

BACKGROUND:

AnWj is a high-incidence blood group antigen associated with three clinical disorders: lymphoid malignancies, immunologic disorders, and autoimmune hemolytic anemia. The aim of this study was to determine the genetic basis of an inherited AnWj-negative phenotype.

METHODS:

We identified a consanguineous family with two AnWj-negative siblings and 4 additional AnWj-negative individuals without known familial relationship to the index family. We performed exome sequencing in search for rare homozygous variants shared by the two AnWj-negative siblings of the index family and searched for these variants in the four non-related AnWj-negative individuals.

RESULTS:

Exome sequencing revealed seven candidate genes that showed complete segregation in the index family and for which the two AnWj-negative siblings were homozygous. However, the four additional non-related AnWj-negative subjects were homozygous for only one of these variants, rs114851602 (R320Q) in the SMYD1 gene. Considering the frequency of the minor allele, the chance of randomly finding 4 consecutive such individuals is 2.56 × 10-18 .

CONCLUSION:

We present genetic and statistical evidence that the R320Q substitution in SMYD1 underlies an inherited form of the AnWj-negative blood group phenotype. The mechanism by which the mutation leads to this phenotype remains to be determined.

KEYWORDS:

AnWj; R320Q; SMYD1; blood group antigen; exome sequencing; hematopoiesis; lymphoproliferative diseases; red cell disorders

PMID:
29956848
DOI:
10.1111/ejh.13133
[Indexed for MEDLINE]

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