Fig. 2: Identification of likely pathogenic variants in PIGS.

a Pedigrees of the 2 families and electrophoregrams of the index cases, parents, and sibs when available. b Brain magnetic resonance image (MRI) of patients with PIGS variants: A, B: P14 (3 years): midsagittal T1- and coronal T2-weighted sequences showing diffuse enlarged folium of the entire cerebellum with a slight enlargement of the fourth ventricle. C, D, E, F: MRI of two further sibs (from the replication cohort) with a PIGS likely pathogenic variant. C, D: Younger brother at 2 years: midsagittal T1- and coronal T2-weighted sequences showing diffuse enlarged folium of the entire cerebellum and marked enlargement and opening of the fourth ventricle. E, F: Older brother at 4 years: midsagittal T1- and coronal T2-weighted sequences showing slight enlarged folium of the entire cerebellum with a slight enlargement of the fourth ventricle. c Evolutionary conservation of the two amino acids affected by the substitution variants. The positions of the variants are indicated in red. The blue rectangle shows the position of the first transmembrane domain. d Flow cytometry of GPI-linked antigens (fresh blood). The left panel reports quantitative data of cell surface expression for 3 GPI-anchored proteins (CD24, CD14, and CD58). Black squares represent the mean fluorescence intensity (MFI) in the 5 healthy controls children (means ± SD) and red squares represent the MFI in patient P14. CD24, CD14, and CD58 expression was respectively decreased in patient P14 by 5.49, 2.99, and 1.44 as compared with the mean (n = 5) of normal samples. The right panel illustrates overlay of CD24 expression on normal B lymphocytes (black histogram) and on P14 B lymphocytes (red histogram)