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Einwärts gerichteter Kalium-Kanal, Subfamilie J, Typ 11

Das Protein, welches von diesem Gen kodiert wird, ist ein Kaliumkanal, der für die Steuerung der Insulinsekretion in den pankreatischen Betazellen verantwortlich ist. Bei loss-of-function Mutationen kommt es zu einer autosomal rezessiven oder seltener dominanten hyperinsulinämischen Hypoklykämie. Dagegen führen aktivitätssteigernde Mutationen zu einem autosomal dominantem permanenten neonatalen oder jugendlichen (MODY13) Diabetes mellitus, der gelegentlich mit neurologischen Symptomen vergesellschaftet sein kann und dann als DEND-Syndrom bezeichnet wird.

Gentests:

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 25 Tage
Probentyp genomische DNS

Verknüpfte Erkrankungen:

Hyperinsulinämische Hypoglycämie 2
KCNJ11
Permanenter neonataler Diabetes mellitus
ABCC8
DEND-Syndrom
KCNJ11
GCK
INS
KCNJ11
Phosphoribosylpyrophosphat-Synthetase-Überaktivität
PRPS1
Wolcott-Rallison-Syndrom
EIF2AK3
Transienter neonataler Diabetes mellitus 3
KCNJ11
DEND-Syndrom
KCNJ11
MODY13 Diabetes
KCNJ11

Referenzen:

1.

Proks P et al. (2004) Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.

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2.

Thomas P et al. (1996) Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy.

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3.

Nestorowicz A et al. (1997) A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism.

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4.

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5.

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6.

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7.

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8.

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9.

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12.

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13.

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17.

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18.

Lin YW et al. (2008) Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism.

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19.

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20.

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21.

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22.

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24.

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26.

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27.

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28.

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29.

Scott LJ et al. (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.

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30.

Zeggini E et al. (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

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31.

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32.

Massa O et al. (2005) KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.

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33.

Proks P et al. (2005) A gating mutation at the internal mouth of the Kir6.2 pore is associated with DEND syndrome.

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34.

Gloyn AL et al. (2006) KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features.

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35.

Masia R et al. (2007) An ATP-binding mutation (G334D) in KCNJ11 is associated with a sulfonylurea-insensitive form of developmental delay, epilepsy, and neonatal diabetes.

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36.

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37.

Sumnik Z et al. (2007) Sulphonylurea treatment does not improve psychomotor development in children with KCNJ11 mutations causing permanent neonatal diabetes mellitus accompanied by developmental delay and epilepsy (DEND syndrome).

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38.

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39.

Koster JC et al. (2008) The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and motor dysfunction in adulthood that is improved with sulfonylurea therapy.

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40.

Slingerland AS et al. (2008) Sulphonylurea therapy improves cognition in a patient with the V59M KCNJ11 mutation.

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41.

Koster JC et al. (2008) DEND mutation in Kir6.2 (KCNJ11) reveals a flexible N-terminal region critical for ATP-sensing of the KATP channel.

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42.

Della Manna T et al. (2008) Glibenclamide unresponsiveness in a Brazilian child with permanent neonatal diabetes mellitus and DEND syndrome due to a C166Y mutation in KCNJ11 (Kir6.2) gene.

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43.

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44.

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45.

Pinney SE et al. (2008) Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations.

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46.

de Lonlay P et al. (1997) Somatic deletion of the imprinted 11p15 region in sporadic persistent hyperinsulinemic hypoglycemia of infancy is specific of focal adenomatous hyperplasia and endorses partial pancreatectomy.

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47.

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48.

NCBI article

NCBI 3767 external link
49.

OMIM.ORG article

Omim 600937 external link
50.

Orphanet article

Orphanet ID 122787 external link
Update: 14. August 2020
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