Nonclassical FD mutations
| Mutant . | Serum ferritin, µg/L . | Transferrin saturation, % . | Examples of pathological findings . | References . | Adult patients, n . |
|---|---|---|---|---|---|
| WT | 15-200 F | 15-45 both | 11 | ||
| 40-300 M | M and F | ||||
| C326Y* | 481-552F | 94-80 F | 11 | 2 F, 2 M | |
| 4232-4326 M | 96-100 M | ||||
| C326S* | Elevated | Elevated | Cirrhosis and arthritis | 12 | 1 M† |
| Y501C* | 43-199 F | 35-64 F | Asthenia, arthralgia, and hepatomegaly | 13 | 2 F, 2 M |
| 568-642 M | 94-104 M | ||||
| D504N* | 1514-1605 M | 89-102 M | Hepatomegaly | 14 | 2 M |
| N144D* | 7500 F | 99 M | Iron loading in hepatocytes and BDECs, cirrhosis | 15 | 1 F, 1 M |
| 10 510 M | |||||
| V72F* | 27-174 F | 31-35 F | Iron loading primarily in hepatocytes, but also in Kupffer cells, BDECs, and PTMs, fibrosis, and hepatic steatosis | 16 | 2 F, 3 M |
| 195-1091 M | 53-81 M | ||||
| Y64N‡ | 176-513 F | 47-86 F | Iron loading in Kupffer cells and hepatocytes, fatigue and tremors | 17 | 3 F, 5 M |
| 647-2,812 M | 91-98 M | ||||
| H507R‡ | 233 F | 46 F | Iron loading in hepatocytes, mild steatosis, and siderosis | 18, 19 | 1 F, 3 M |
| 785-3751 M | 93-100 M | ||||
| S71F‡ | 5500 | 70 | Uncharacterized | 20 | 1§ |
| G204S‡ | 4-5236 F | 2-100 F | Mixed iron loading, but mainly hepatocytes heterogeneous phenotype | 20, 21 | 3 F, 5 M |
| 508-3755M | 27-91 M | ||||
| D270V‡ | <1000 F | 78 F | Fatigue, fibrosis, iron loading in hepatocytes and Kupffer cells, hepatitis C | 22, 23 | 1 F, 1 M |
| 353-559 M|| | 37-41 M|| | ||||
| S338R‡ | 1990 M | 90 M | Iron loading in hepatocytes, Kupffer cells, and PTMs, mild steatosis | 24 | 1 M |
| Mutant . | Serum ferritin, µg/L . | Transferrin saturation, % . | Examples of pathological findings . | References . | Adult patients, n . |
|---|---|---|---|---|---|
| WT | 15-200 F | 15-45 both | 11 | ||
| 40-300 M | M and F | ||||
| C326Y* | 481-552F | 94-80 F | 11 | 2 F, 2 M | |
| 4232-4326 M | 96-100 M | ||||
| C326S* | Elevated | Elevated | Cirrhosis and arthritis | 12 | 1 M† |
| Y501C* | 43-199 F | 35-64 F | Asthenia, arthralgia, and hepatomegaly | 13 | 2 F, 2 M |
| 568-642 M | 94-104 M | ||||
| D504N* | 1514-1605 M | 89-102 M | Hepatomegaly | 14 | 2 M |
| N144D* | 7500 F | 99 M | Iron loading in hepatocytes and BDECs, cirrhosis | 15 | 1 F, 1 M |
| 10 510 M | |||||
| V72F* | 27-174 F | 31-35 F | Iron loading primarily in hepatocytes, but also in Kupffer cells, BDECs, and PTMs, fibrosis, and hepatic steatosis | 16 | 2 F, 3 M |
| 195-1091 M | 53-81 M | ||||
| Y64N‡ | 176-513 F | 47-86 F | Iron loading in Kupffer cells and hepatocytes, fatigue and tremors | 17 | 3 F, 5 M |
| 647-2,812 M | 91-98 M | ||||
| H507R‡ | 233 F | 46 F | Iron loading in hepatocytes, mild steatosis, and siderosis | 18, 19 | 1 F, 3 M |
| 785-3751 M | 93-100 M | ||||
| S71F‡ | 5500 | 70 | Uncharacterized | 20 | 1§ |
| G204S‡ | 4-5236 F | 2-100 F | Mixed iron loading, but mainly hepatocytes heterogeneous phenotype | 20, 21 | 3 F, 5 M |
| 508-3755M | 27-91 M | ||||
| D270V‡ | <1000 F | 78 F | Fatigue, fibrosis, iron loading in hepatocytes and Kupffer cells, hepatitis C | 22, 23 | 1 F, 1 M |
| 353-559 M|| | 37-41 M|| | ||||
| S338R‡ | 1990 M | 90 M | Iron loading in hepatocytes, Kupffer cells, and PTMs, mild steatosis | 24 | 1 M |
Based on the literature, the 12 Fpn mutations listed in the table are associated with elevated serum ferritin and transferrin saturation, although not every subject carrying the mutation had abnormal biochemical parameters or related pathology. Adult = ≥ 18 years.
BDEC, bile duct epithelial cell; F, female; M, male PTM, portal tract macrophage.
Mutants in which hepcidin binding is impaired based on the results of our study; of these, C326Y, C326S, Y501C, D504N, and N144D were more severely impaired.
Six descendants aged 8 to 16 had transferrin saturation 84-97%.
Mutants in which hepcidin binding is normal, but hepcidin-mediated ubiquitination is impaired based on the results of our study; of these, Y64N and H507R were most severely impaired, followed by S71F and G204S.
Source did not cite sex.
The patient’s parameters were recorded at 2 different times.