三名具有路德血型无效表型个体的LU基因中存在不同的失活突变。

Different inactivating mutations in the LU genes of three individuals with the Lutheran-null phenotype.

作者信息

Karamatic Crew Vanja, Mallinson Gary, Green Carole, Poole Joyce, Uchikawa Makoto, Tani Yoshihiko, Geisen Christof, Oldenburg Johannes, Daniels Geoff

机构信息

Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK.

出版信息

Transfusion. 2007 Mar;47(3):492-8. doi: 10.1111/j.1537-2995.2006.01141.x.

DOI:10.1111/j.1537-2995.2006.01141.x

PMID:17319831

Abstract

BACKGROUND

The null phenotype of the Lutheran blood group system, Lu(null) or Lu(a-b-), is characterized by the lack of all Lutheran system antigens. It can arise from three genetic backgrounds: recessive, dominant, or X-linked. Lu(null) of the recessive type appears to result from homozygosity for an inactive LU gene.

STUDY DESIGN AND METHODS

Three unrelated recessive Lu(null) individuals were assessed by standard serologic tests. All exons of the LU gene were directly sequenced from amplified genomic DNA. The validity of the observed mutations within the LU gene was confirmed by the use of either restriction enzymes or allele-specific primers.

RESULTS

All three individuals had the serologic characteristics of recessive Lu(null). One individual was doubly heterozygous for a nonsense mutation 691C>T in exon 6 (Arg231STOP) and a deletion of LU exons 3 and 4. The other two samples showed homozygous nonsense mutations: one had 711C>A in exon 6 (Cys237STOP) and the other 361C>T in exon 3 (Arg121STOP).

CONCLUSIONS

The results revealed four unique genetic backgrounds from three examples of the rare recessive Lu(null) phenotype, each encoding Lutheran glycoproteins with a disrupted structure.

摘要

背景

路德血型系统的无效表型，即Lu(null) 或Lu(a-b-)，其特征是缺乏所有路德系统抗原。它可源于三种遗传背景：隐性、显性或X连锁。隐性类型的Lu(null) 似乎是由无活性LU基因的纯合性导致的。

研究设计与方法

通过标准血清学检测对三名无关的隐性Lu(null) 个体进行评估。从扩增的基因组DNA中直接对LU基因的所有外显子进行测序。通过使用限制性内切酶或等位基因特异性引物来确认LU基因内观察到的突变的有效性。

结果

所有三名个体都具有隐性Lu(null) 的血清学特征。一名个体在第6外显子中存在691C>T的无义突变（Arg231STOP）以及LU外显子3和4的缺失，呈双重杂合状态。另外两个样本显示为纯合无义突变：一个在第6外显子中有711C>A（Cys237STOP），另一个在第3外显子中有361C>T（Arg121STOP）。