Functional studies on patients with FNIP1 deficiency. (A) Schematic illustration displaying the interaction of FNIP1 in B cells. Positive and negative regulators of mTORC1 signaling are depicted in green and in blue, respectively. Folliculin and Fnip1/2 have been described as both positive and negative regulators of mTORC1. (B) Pedigrees showing 3 families with affected individuals harboring FNIP1 variants. Solid symbols indicate affected persons who were homozygous or compound heterozygous for the mutant alleles; half solid symbols, heterozygous persons; circles, female family members; square, male family members; double lines, consanguinity. (C) Expression of FNIP1 messenger RNA in P1 (quantitative reverse-transcription polymerase chain reaction analysis). Data are expressed as mean ± standard deviation (2 independent experiments, each performed in triplicate). Statistical analysis was performed using 1-way analysis of variance. (D) FNIP1 protein expression in T cells. (E) Bone marrow B-cell immunophenotyping in P1 compared with a healthy control and 1 Bruton tyrosine kinase (BTK) patient (representative experiment). (F) Quantification of total mitochondrial abundance and mitochondrial activity in circulating CD19⁺ cells isolated from an healthy control and P1 (representative experiment). AU, arbitrary units. (G) Evaluation of pAKT, pS6, and p4EBP1 levels in B-cell bone marrow progenitors from P1 and a healthy control (2 experiments). In all graphs, **P < .01 and ***P < .001. Data are presented as means ± standard deviation. AMP, adenosine 5′-monophosphate; ATP, adenosine triphosphate; HC, healthy control; WT, wild type.