Page 206 - 2019_03-Haematologica-web

T. Shahin et al.
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Figure 1. Identification of a novel IL6ST variant in PP498L. (A) Pedigree of PP498L showing consanguinity in the family. PP498L has 3 deceased siblings, a sister, and twin brothers [one who died in utero (III-3)], and a brother who has congenital blindness of unknown etiology but is unremarkable for his immune system. PP498L is homozy- gous for IL6ST c.1493C>T (p.P498L/p.P498L). (B) X-ray images of PP498L showing scoliosis (left), scaphocephaly (top right), edema in the right ankle (bottom center), and flexion contractures of the small joints in the hand (bottom right). (C) Flow cytometry plot illustrating a reduction in CD19+ B cells and normal CD3+ T cells in PBMCs of PP498L at the of age 12.4 years. (D) Sanger sequencing of the identified IL6ST variant (c.1493C>T) in PP498L and family members. (E) Linear representation of GP130 and crystal structure of the GP130-IL6-IL6Rα complex (adapted and modified5) outlining the protein domains and the two mutations found in PP498L and the previously described patient (PN404Y ; p.N404Y). D: domains; TM: transmembrane domain; CT: cytoplasmic tail. (F) Conservation of the amino acid proline at posi- tion 498 across species including some adjacent amino acids. (G) Flow cytometry analysis of GP130 expression in fibroblasts of PP498L compared to that of a healthy donor. Average of mean fluorescence intensity (MFI) from 2-3 technical replicates is shown on the top right area of the graphs.
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haematologica | 2019; 104(3)