Clinical phenotype of a patient with NFAT1 deficiency, joint contractures, and B-cell malignancy. (A) Radiograph demonstrating the extent to which knees could be straightened, documenting the fixed flexion deformity. (B) Osteochondroma (arrow) on the anterior aspect of the right proximal fibula. (C) Hematoxylin and eosin (H&E) stain and CD20, CD21, CD30, BCL2, and BCL6 immunostain of a patient lymph node biopsy. Scale bars for H&E, CD20, CD30, BCL6, and BCL2 are 50 μm, and that for CD21 is 3 mm. (D) Family pedigree. Half-filled symbols represent heterozygous unaffected individuals, filled symbols represent homozygous affected individual; arrow represent proband; question marks represent ungenotyped. (E) Sanger sequencing of DNA extracted from whole blood of the patient, family members, and a healthy control. Site of 4–base-pair deletion is indicated. (F) Schematic illustrating the protein domains of NFAT1. Location of variant is shown in red. Affected region was aligned to other species. Asterisks indicate full conservation. (G) Schematic illustrating ionomycin-induced activation of calcineurin and NFAT1. (H) NFATC2 transcript abundance relative to β-actin (ACTB) in the patient (II-1), a heterozygous control (II-2), and a healthy control (HC) determined by quantitative PCR. Red diamonds, II-1; blue circles, II-2; green circles, HC. ∗∗P < .01, ∗∗∗∗P< .0001, one-way analysis of variance and Tukey’s post hoc test. (I) Immunoblot of patient (II-1), heterozygous control (II-2), and control-derived LCLs using an N-terminal NFAT1 antibody before and after 10 minutes of ionomycin stimulation with or without FK506 treatment (n = 3).