Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

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.

Diagnostik:

Clinic Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5
Probentyp genomic DNA
Clinic Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 25
Probentyp genomic DNA
Clinic Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 20
Probentyp genomic DNA
Clinic Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25
Probentyp genomic DNA

Krankheiten:

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.

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2.

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3.

Koster JC et al. (2000) Targeted overactivity of beta cell K(ATP) channels induces profound neonatal diabetes.

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4.

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5.

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6.

Gloyn AL et al. (2004) Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.

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7.

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8.

Henwood MJ et. al. (2005) Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.

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9.

Laukkanen O et. al. (2004) Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study.

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11.

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Gupta RK et al. (2005) The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion.

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14.

Yorifuji T et al. (2005) The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus.

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Hansen SK et. al. (2005) Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.

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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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18.

Proks P et al. (2005) Functional effects of KCNJ11 mutations causing neonatal diabetes: enhanced activation by MgATP.

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19.

Colombo C et al. (2005) Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation.

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Slingerland AS et al. (2006) Activating mutations in the gene encoding Kir6.2 alter fetal and postnatal growth and also cause neonatal diabetes.

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22.

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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23.

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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24.

et al. (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

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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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27.

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28.

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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29.

Mlynarski W et al. (2007) Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11.

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30.

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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31.

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

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32.

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

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33.

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

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34.

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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35.

Girard CA et al. (2009) Expression of an activating mutation in the gene encoding the KATP channel subunit Kir6.2 in mouse pancreatic beta cells recapitulates neonatal diabetes.

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36.

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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37.

Taneja TK et al. (2009) Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism.

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38.

Mohamadi A et al. (2010) Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15-yr-old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM.

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39.

Clark RH et al. (2010) Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in origin.

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40.

Inagaki N et. al. (1995) Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.

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41.

Chandy KG et al. (1993) Nomenclature for mammalian potassium channel genes.

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42.

Inagaki N et al. (1996) A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels.

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43.

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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44.

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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45.

Miki T et al. (1997) Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel.

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46.

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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47.

Hani EH et al. (1998) Missense mutations in the pancreatic islet beta cell inwardly rectifying K+ channel gene (KIR6.2/BIR): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians.

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