Dieses Gen kodiert einen wichtigen Faktor der Komplementkaskade. Mutationen sind für verantwortlich für das atypische hämolytisch urämische Syndrom, die membranoproliferative Glomerulonephritis und die altersabhängige Makuladegeneration.
Zuverlässige epidemiologische Daten zur Mutationshäufigkeit und -lokalisation liegen nicht vor. Mutationen dieses Gens scheinen in allen Rassen vorzukommen.
Das Gen HF1, welches auch als beta1-H bekannt ist, besitzt eine Größe von 96 kb. In unmittelbarer Nachbarschaft befinden sich auf dem selben Chromosom 4 immunologisch und strukturell ähnliche Proteine (FHR1-4). Das Gen wird von 22 Exons gebildet.
Mutationen dieses Gens wurden in einigen, allerdings nicht in allen, Familien mit familiärem Hämolytisch Urämischem Syndrom (HUS) gefunden. Weiterhin wurde eine Assoziation von Gendefekten mit der Nierenbeteiligung bei systemischem Lupus erythematodes, Typ 2 Membranoproliferativer Glomerulonephritis und Kollagen III Glomerulopathie beobachtet.<br>Die Polymorphismen I62V und Y402H erhöhen das Risiko an altersbedingter Makuladegeneration zu erkranken.
Das Translationsprodukt ein Serumglykoprotein wird vornehmlich von der Leber sezerniert. Das Protein besteht aus 1309 Aminosäuren und besitzt im vollglykosilierten Zustand ein Molekulargewicht von 159 kD. Die Aminosäurenkette besteht aus 20 repetitiven Einheiten von jeweils 60 Aminosäuren, die als kurze konsensus Repeats (SCR) bezeichnet werden. Die Tertiärstruktur gleicht einem Griechischen Buchstaben a. Das Protein bindet polyanionische Zelloberflächen und C3b. Hierdurch begünstigt es den Abbau von C3b und damit eine Unterbrechung des alternativen Weges der Komplementaktivierung. Niedrige Plasmaspiegel von Faktor H führen zur Reduktion von C3 als Folge eines gesteigerten Verbrauches in einer ungezügelten Aktivierung.
Eine bezüglich HUS belastete Familienanamnese, ein rezidivierender Verlauf und niedrige HF1 Spiegel könnten die Indikation für eine molekulargenetische Untersuchung begründen. Weiterhin könnte eine molekulargenetische Untersuchung bei familiärer Häufung von Nierenbeteiligung bei Lupus erythematode, Typ 2 Mesangioproliferativer Glomerulonephritis und Kollagen III Glomerulopathie erwogen werden.
Insbesondere Mutationen in den Exons 18-20 scheinen eine pathogenetische Bedeutung zu besitzen. Patienten mit einer nachgewiesenen Mutation haben eine schlechte Prognose nach Nierentransplantation. In 50-90% der Fälle kommt es zu einem Wiederauftretender Grunderkrankung und in 80-90% dieser Rezidive ist ein Transplantatverlust die Folge. Eine wesentlich bessere Prognose scheinen kombinierte Nieren- und Lebertransplantationen zu haben. Patienten mit nachgewiesener Mutation sollten für eine Supplemenation mit rekombinantem Faktor H vorgesehen werden. Eine Familienuntersuchung zur Risikoabschätzung könnte in Einzelfällen erwogen werden.
Klinisch | Untersuchungsmethoden | Familienuntersuchung |
Bearbeitungszeit | 5 Tage | |
Probentyp | genomische DNS |
Klinisch | Untersuchungsmethoden | Hochdurchsatz-Sequenzierung |
Bearbeitungszeit | 25 Tage | |
Probentyp | genomische DNS |
Klinisch | Untersuchungsmethoden | Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens |
Bearbeitungszeit | 20 Tage | |
Probentyp | genomische DNS |
Klinisch | Untersuchungsmethoden | Multiplex ligationsabhängige Amplifikation |
Bearbeitungszeit | 20 Tage | |
Probentyp | genomische DNS |
1. |
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2. |
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3. |
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5. |
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12. |
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46. |
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48. |
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49. |
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50. |
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53. |
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56. |
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70. |
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75. |
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81. |
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NCBI article NCBI 3075 |
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OMIM.ORG article Omim 134370 |
84. |
Orphanet article Orphanet ID 119363 |