PDF(Pubmed)
Abstract：
Germline variants in the phosphatidylinositol glycan class A (PIGA) gene, which is involved in glycosylphosphatidylinositol (GPI) biosynthesis, cause multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2) with X-linked recessive inheritance. The available literature has described a pattern of almost 100% X-chromosome inactivation in mothers carrying PIGA variants. Here, we report a male infant with MCAHS2 caused by a novel PIGA variant inherited from his mother, who has a non-skewed pattern of X inactivation. Phenotypic evidence supporting the pathogenicity of the variant was obtained by flow-cytometry tests. We propose that the assessment in neutrophils of the expression of GPI-anchored proteins (GPI-APs), especially CD16, should be considered in cases with variants of unknown significance with random X-inactivation in carrier mothers in order to clarify the pathogenic role of PIGA or other gene variants linked to the synthesis of GPI-APs.
摘要：
磷脂酰肌醇聚糖A类（PIGA）基因中的种系变体，参与糖基磷脂酰肌醇（GPI）的生物合成，导致多种先天性异常-张力减退-癫痫发作综合征2（MCAHS2），并伴有X连锁隐性遗传。现有文献已经描述了携带PIGA变体的母亲中几乎100%X染色体失活的模式。这里,我们报道了一名男性婴儿MCAHS2，由他母亲遗传的一种新的PIGA变异体引起，具有X失活的非偏斜模式。通过流式细胞术测试获得了支持该变体致病性的表型证据。我们建议在中性粒细胞中评估GPI锚定蛋白（GPI-AP）的表达，在携带者母亲中具有未知意义的变异并随机X失活的情况下，尤其是CD16，以阐明PIGA或与GPI-AP合成相关的其他基因变异的致病作用。
