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T.K. Bariana et al.
Platelet studies
Aggregation and transmission electron microscopy (EM) studies were performed as described previously.10
Metabolic profiling
Global metabolic profiling of plasma was performed by Metabolon Inc. (Durham, NC, USA) using the DiscoveryHD4 liq-
uid chromatography tandem mass spectrometry (LC-MS/MS) platform, as previously described.11 Results of study participants were compared with 496 subjects between the ages of 4 and 55 years without thrombocytopenia. A separate LC-MS platform method, previously described,12,13 was used for specific confirma- tion of the global sphingolipid profile. Further details are provided in the Online Supplementary Methods.
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Figure 2. Clinical characteristics associated with loss-of-function KDSR variants. (A) Pedigree and variants identified in KDSR. ‘+’ denotes the major allele. The propositus and affected sibling, but not the healthy sibling, carry the missense variant 18:61018270 G>A (p.Arg154Trp) and the nonsense variant 18:61006104 G>A (p.Arg236*). Co-segregation analysis demonstrated that the father carries the former and the mother the latter variant. (B) Serial blood counts are shown for the two affected siblings and a single value for the healthy brother. Fluctuating anemia and thrombocytopenia was observed, without evidence of neutropenia. (C) Bone marrow biopsy. (Left) Numerous dysplastic megakaryocytes made visible with linker for activation of T cell (LAT) staining are present. (Right) Marrow fibrosis with strong stromal reticulin staining. Magnification x40. Further images can be found in the Online Supplementary Appendix. (D) The affected sibling was born dur- ing the course of this study and presented at birth with thrombocytopenia and mild ichthyosis in her left axilla. The skin symptoms improved spontaneously over the first month. (E) Platelets were examined by electron microscopy for an unrelated healthy control, the propositus, and the affected sibling. There were no marked morphological differences. Arrowed magnifications show delta granules. Magnification x 12,000.
1038
haematologica | 2019; 104(5)
Hemoglobin