Pedigrees and genetics of families carrying PTPN2 mutations. (A) Anatomopathological section of liver biopsy showing lesions of chronic hepatitis and cholangitis (Metavir A3F3) with an inflammatory infiltrate compatible with a lupus-type autoimmune etiology. Hematoxylin-eosin saffron staining: portal tract inflammatory infiltrate with lymphoid follicles (*) and piecemeal necrosis (arrows). HGVS, Human Genome Variation Society. (B) cDNA mutations, GnomAD allele frequency (v2.1), and CADD score. (C) Family pedigrees with probands indicated by A1, B1, C1, D1, E1, F1. Squares: males; circles: females; black: affected mutation carriers; grey: unaffected mutation carriers. WT: WT PTPN2 allele. Under each patient is the genotype at the specified locus. (D) Linear protein model showing the location of the described PTPN2 variants (represented in bold) together with previously published variants (in grey). Multiple alignments of PTPN2 orthologs from different species using the Clustal Omega software. The affected amino acid for Y126N is boxed in red. Residues corresponding to bipartite NLS are underlined. TC, T cell. (E) cDNA from EBV-transformed B cells of patient D1 and one HC were amplified around exon 2. Migration and sequencing of PCR products are represented along with the expected result of RNA translation with exon 2 skipping. Source data are available for this figure: SourceData F1.