Krawitz et al. (2013) reported a Caucasian woman who was diagnosed with hemolytic anemia with a negative direct antiglobulin test at age 44 years. She experienced frequent hemolytic crises, abdominal pain, diarrhea, headache, arthralgia, dyspnea, and fatigue for ... Krawitz et al. (2013) reported a Caucasian woman who was diagnosed with hemolytic anemia with a negative direct antiglobulin test at age 44 years. She experienced frequent hemolytic crises, abdominal pain, diarrhea, headache, arthralgia, dyspnea, and fatigue for several year thereafter. Flow cytometric analysis of the patient at age 49 years showed reduced expression of GPI-anchored proteins on blood cells. She was treated with the complement inhibitor eculizumab with improvement of the clinical features. Medical history revealed that she had cold-induced urticaria in childhood and later had episodic urticaria without exposure to cold, which was sometimes accompanied by systemic symptoms.
In a woman with paroxysmal nocturnal hemoglobinuria, Krawitz et al. (2013) identified a heterozygous germline splice site mutation in the PIGT gene (610272.0002). The mutation was found by targeted enrichment of all exons of genes involved in GPI ... In a woman with paroxysmal nocturnal hemoglobinuria, Krawitz et al. (2013) identified a heterozygous germline splice site mutation in the PIGT gene (610272.0002). The mutation was found by targeted enrichment of all exons of genes involved in GPI anchor synthesis followed by deep sequencing, and it was confirmed by Sanger sequencing. Array CGH on patient peripheral cells showed that a large proportion of granulocytes also carried a somatic heterozygous 8-Mb deletion of chromosome 20q11.23-q13.12, including the PIGT gene. Transfection of the splice site mutation into Pigt-null CHO cells caused only a minor increase in CD55 (125240) surface expression but almost no CD59 (107271) expression, suggesting a loss of function. The findings suggested that 2 hits in the PIGT gene, 1 germline and 1 somatic in hematopoietic stem cells, are necessary for development of the disorder.