A 15-year-old male patient with chief complaint of pain and swelling of left knee and right ankle was admitted at hospital. Apparent articular symptoms began 1 year before the admission and they were progressive, causing limited mobility for the patient. Fatigue, persistent fever, and morning stiffness were the other chronic significant complaints of the patient. He suffered from obvious symptoms and signs of mental involvement caused by a delayed mental development. He had delayed neurological development. In physical examination, weight for age and height for age were under third percentile. Mild microcephaly, high arch palate, fish mouth, cervical lymphadenopathy, lack of sexual maturation, hypotonia, increased patellar deep tendon reflex (DTR), deformity of lower limbs (thick and floppy), and decreased range of motion of both knees were found. In his past medical history, patient had chronic intermittent fever since his infancy. Magnetic resonance imaging without contrast revealed a severe articular effusion. Ophtalmologic examination showed corneal nerve enlargement and evidences of old iritis and uveitis. Main laboratory findings were increased ESR (erythrocyte sedimentation rate; 65 mm Hg/h; normal = 0-22), positive CRP (c-reactive protein; 35 mg/L; normal: 0-3), semiclear urine, without proteinuria. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone levels were lower than normal range, but serum growth hormone level was in normal range. Antinuclear antibody (ANA) and anticyclic citrullinated peptide (anti-CCP) were all negative. Finally, genetic studies based on Sanger-based PCR-sequencing of the entire coding region (including splicing sites) showed a heterozygous variant NM_001243133: c.785G>A (NP_001230062: p.Arg262Gln) in Exon 3 of NLRP3 gene, which confirmed the diagnosis of CAPS. The noted variant has not been reported yet, and it has been registered as a new NLRP3 gene mutation in the database of International Society for Systemic Auto Inflammatory Diseases (as c.779G>A; p.R260Q). The detected variant has not been previously reported for its pathogenicity. However, multiple lines of in silico computational analysis (Mutation Taster, CADD, etc) support the deleterious effect of the variant on the gene or gene product(s). The variant is absent in population databases (ExAC, 1000G, etc). Two years later, swelling and nodularity of thyroid was detected during an outpatient visit. Further investigations revealed an elevated serum level of calcitonin (86/7 pg/mL) and T4 (228 nmol/L) in spite of low thyroid stimulating hormone (TSH; 0/07 mIU/mL). Thyroid scan showed multinodular goiter with 2 cold nodules in right lobe and increased uptake in the remainder of thyroid gland. Biopsies taken showed medullary carcinoma of thyroid. Sequence of 2 genes related with thyroid cancer (RET and NTRK1) was enriched and sequenced by high-throughput platform. All exons and flanking 10 bp were detected and analyzed. Detected variations include the following: single-point mutation and small Indel (within 20 bp). Large duplication and deletion, balanced translocation, inversions, ploidy changes, uniparental disomy, and methylation alterations cannot be detected by this test. One heterozygous variant in Exon 16 of RET gene (NM_020975: c.2753T>C; NP_066124: p. Met918Thr) that has been previously reported for its pathogenicity were found. Two homozygous variants (c.337+9G>A and c.2071G>A; p. Gly691Ser) that have been reported as benign variants (polymorphism) were determined, as well. The presence of the mutation c.2753T>C has been confirmed using Sanger-based PCR-sequencing ().