Wiskott-Aldrich Syndrome in a Girl Caused by Heterozygous WASP Mutation and Extremely Skewed X-Chromosome Inactivation: A Novel Association with Maternal Uniparental Isodisomy 6
Wiskott-Aldrich Syndrome in a Girl Caused by Heterozygous WASP Mutation and Extremely Skewed X-Chromosome Inactivation: A Novel Association with Maternal Uniparental Isodisomy 6
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DOI：
10.1159/000370059
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发表时间：
2015-01-01
期刊：
影响因子：
2.5
通讯作者：
Hara, Toshiro
中科院分区：
文献类型：
--
作者：
Takinnoto, Tonnohito;Takada, Hidetoshi;Hara, Toshiro
Wiskott-Aldrich综合征（WAS）是一种X连锁疾病，其特征是微血小板减少症、湿疹和免疫缺陷，主要由WASP（Wiskott-Aldrich综合征蛋白）基因突变引起。女性携带者通常无症状，因为其造血细胞中正常的、未突变的X染色体优先激活。我们报告我们的观察与WAS的女孩，谁表现出先天性血小板减少症的症状。WASP基因的DNA测序分析显示，在外显子10杂合无义突变。WASP和正常WASP mRNA表达缺失。我们发现优先失活的X染色体上的野生型WASP位于。单核苷酸多态性微阵列检测和串联重复区多态性可变数目的分析揭示了6号染色体的母系单亲同二体性。我们的研究结果强调了WASP评估在女性先天性血小板减少症中的重要性，并表明，WASP 6可能与非随机X染色体失活的病理生理学有关。(C)2015 S. Karger AG，巴塞尔
Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by microthrombocytopenia, eczema and immune deficiency, caused primarily by mutations in the WASP (Wiskott-Aldrich syndrome protein) gene. Female carriers are usually asymptomatic because of the preferential activation of the normal, nonmutated X-chromosome in their hematopoietic cells. We report our observations of a female child with WAS, who displayed symptoms of congenital thrombocytopenia. DNA sequencing analysis of the WASP gene revealed a heterozygous nonsense mutation in exon 10. The expressions of WASP and normal WASP mRNA were defective. We found preferential inactivation of the X-chromosome on which wild-type WASP was located. Single-nucleotide polymorphism microarray testing and the analysis of the polymorphic variable number of tandem repeat regions revealed maternal uniparental isodisomy of chromosome 6 (UPD6). Our results underscore the importance of WASP evaluation in females with congenital thrombocytopenia and suggest that UPD6 might be related to the pathophysiology of nonrandom X-chromosome inactivation. (C) 2015 S. Karger AG, Basel