Number Age/sex Hb (g/L) EPO (IU/L) Relevant clinical data Mode of inheritance Associated mutations Relation to protein structure Protein changes and mutation15 ]) Reference 1 43 (44) M 202 24.0 (5–25) N/A N/A Homozygous JAK2 V617F Substitution between N-terminal MYND zinc finger-like domain and conserved C-terminal catalytic domain p.(Gln157His); Ladroue et al. [6 ] 2 65 (65) M 171 29.0 (5–30) Thrombocytosis, leukocytosis and splenomegaly, Autosomal dominant Homozygous JAK2 V617F Substitution between N-terminal MYND zinc finger-like domain and conserved C-terminal catalytic domain p.(Gln157His); Albiero et al. [16 ] 3 40 (40) M 170 8.0 (5–30) N/A Autosomal dominant None Substitution between N-terminal MYND zinc finger-like domain and conserved C-terminal catalytic domain p.(Gln157His); Albiero et al. [16 ] 4 22 (34) M 179 90.0 (5–25) N/A N/A None Substitution of highly conserved amino acid one residue from site that chelates Zn and Cd ions Mutation causes delayed hydroxylation of HIF-α p.(Pro200Gln); Ladroue et al. [6 ] 5 54 (54) M 192 20.0 (5–25) Inflammatory arthromyalgia, visual symptoms, and phlebotomies Autosomal dominant None Truncation in catalytic domain of 154 C-terminal amino acids p.(Met202Ilefs
Al-Sheikh et al. [17 ] 6 >54 (>54) M 171 11.5 (5–25) Phlebotomies Autosomal dominant None Truncation in catalytic domain of 154 C-terminal amino acids p.(Met202Ilefs Al-Sheikh et al. [17 ] 7 61 (80) M 230 2.0 (5–25) Hemorrhage, phlebotomy, and aspirin N/A JAK2 -exon 12Substitution of highly conserved part of catalytic site p.(Asn203Lys); Albiero et al. [18 ] 8 49 (46) M 200 11.0 (5–25) Cardiac disease N/A None Substitution mutation of catalytic site p.(Lys204Glu);
Bento et al. [19 ] 9 52 (51) M 183 8.13 (5–25) Klinefelter’s syndrome N/A None Truncation mutation of catalytic site p.(Gln221 Lambert, unpublished data (2013) 10 34 (24) M 172 N/A Headaches N/A None Truncation mutation of catalytic site p.(Arg227Alafs Bento and Almeida, unpublished data (2014) 11 16 (60) F 160 40.5 (<31.5) Red eyes, flushed cheeks and feet headache, episodic chest pain palpitations, and primary hyperparathyroidism N/A None Substitution of highly conserved residue site likely to affect protein folding and stability p.(Ala228Ser); Yang et al. [8 ] 12 52 (58) M 178 N/A N/A None Truncation mutation of catalytic site p.(Gln239 Bento and Almeida, unpublished data (2014) 13 25 (48) M 192 2x normal (5–25) N/A N/A None Substitution of highly conserved residue of catalytic site p.(Asp254His); Ladroue et al. [6 ] 14 73 (73) M 188 1.3 (10.2–28.5) Smoker N/A None Loss of catalytic activity of PHD2 protein p.(Leu279Thrfs43 Jang et al. [20 ] 15 22 (22) M 178 N/A Tinnitus N/A None Truncation of 143 C-terminal amino acids p.(Arg281Thrfs Al-Sheikh et al. [17 ] 16 68 (65) M 183 60 (5–25) N/A None Substitution mutation of catalytic site p.(Gly285Arg);
Bento et al. [19 ] 17 29 (38) M 176 5.0 (5–25) N/A Autosomal dominant None Substitution of nonconserved residue of catalytic domain p.(Lys291Ile); Albiero et al. [18 ] 18 48 (48) F 180 6.2 (5–25) Leukoclastic vasculitis N/A None Substitution mutation of catalytic site p.(Pro304Leu); Percy and McMullin, unpublished data (2004) 19 45 (45) M 180 N/A Smoker with intermittent claudication and death from esophageal carcinoma Autosomal dominant None Substitution of highly conserved amino acid, close proximity to site responsible for coordinating Fe2+ at active site p.(Pro317Arg); Percy et al. [2 ] 20 26 (26) F 180 6.3 (5–25) Superficial thrombophlebitis, history of menorrhagia, and phlebotomies Autosomal dominant None Substitution of highly conserved amino acid, close proximity to site responsible for coordinating Fe2+ at active site p.(Pro317Arg); Percy et al. [2 ] 21 30 (30) M 175 6.4 (5–25) Paresthesia, absent left kidney, and enlarged right kidney Autosomal dominant None Substitution of highly conserved amino acid, close proximity to site responsible for coordinating Fe2+ at active site p.(Pro317Arg); Percy et al. [2 ] 22 31 (31) F 174 6.0 (3–34) N/A Autosomal dominant None Substitution of highly conserved amino acid of catalytic domain p.(Trp334Arg); Bento et al. [21 ] 23 49 (55) M 215 8.3 (4–16) Phlebotomies Sister has polycythemia None Truncation in highly conserved amino acid residue in catalytic domain p.(Trp334 (this paper) 24 35 (35) F 178 10.7 (5–25) Phlebotomies N/A None Truncation of 50 C-terminal amino acids p.(Gln337 Al-Sheikh et al. [17 ] 25 21 (24) M 171 9.9 (5–25) TIA N/A None Truncation mutation of catalytic site p.(Val338Glyfs
Bento et al. [19 ] 26 47 (47) M 168 9.5 (5–25) N/A None Substitution mutation of catalytic site p.(Arg371Cys); Percy and McMullin, unpublished data (2013) 27 17 (25) M 191 Normal (5–25) N/A N/A None Substitution of highly conserved amino acid 3 residues away from Fe2+ chelating residue p.(Arg371His); Ladroue et al. [6 ] 28 29 (38) M 188 12.0 (5–25) Sagittal sinus thrombosis and phlebotomies N/A None Substitution of highly conserved amino acid 3 residues away from Fe2+ chelating residue p.(Arg371His); Percy et al. [3 ] 29 30 (43) M 202 18.0 (5–25) Recurrent para-aortic paraganglioma hypertension phlebotomies N/A Homozygous C282Y mutation Substitution of highly conserved amino acid critical to coordinating Fe2+ binding p.(His374Arg); Ladroue et al. [12 ] 30 64 (67) F 161 N/A Suspected liver and renal angiomas Autosomal dominant None Truncation in catalytic domain p.(Arg398 Ladroue et al. [6 ] 31 26 (41) M 193 6.5 (5–25) N/A Autosomal dominant None Truncation in catalytic domain p.(Arg398 Ladroue et al. [6 ] 32 60 (80) M 164 23.0 (5–25) Treated with aspirin and phlebotomies N/A None Substitution of highly conserved residue mutation of catalytic domain p.(Lys423Glu); Albiero et al. [18 ]
