Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Insulin

Das INS-Gen kodiert das Proinsulin, aus welchem durch Proteolyse das Insulin gebildet wird. Das Insulin ist ein wichtiges Hormon der Regulation des Glucosestoffwechsels. Insulinmangel und verminderte Insulinsensitivität führen zum Diabetes Mellitus. Folgende monogene autosomal dominante Erkrankungen werden durch Mutationen dieses Gens hervorgerufen: der permanente neonatale Diabetes und der etwas speter einsetzende MODY-Diabetes von Typ 10. Weitere Insulinabnormalitärten sind Hyperproinsullinämie, Wakayama Insulinämie und andere die auf abnorm aktiviertes Proinsulin beruhen.

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 25
Probentyp genomic DNA
Clinic Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25
Probentyp genomic DNA

Krankheiten:

MODY10 Diabetes
INS
Permanenter neonataler Diabetes mellitus
ABCC8
DEND-Syndrom
KCNJ11
GCK
INS
KCNJ11
PDX1

Referenzen:

1.

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2.

Ueki K et al. (2006) Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes.

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3.

Stead JD et al. (2000) Allele diversity and germline mutation at the insulin minisatellite.

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4.

Jaquet D et al. (2000) Insulin resistance early in adulthood in subjects born with intrauterine growth retardation.

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5.

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6.

Cheung AT et al. (2000) Glucose-dependent insulin release from genetically engineered K cells.

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7.

Dandona P et al. (2001) Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?

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8.

Vafiadis P et al. (2001) Class III alleles of the variable number of tandem repeat insulin polymorphism associated with silencing of thymic insulin predispose to type 1 diabetes.

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9.

Osawa H et al. (2001) Systematic search for single nucleotide polymorphisms in the insulin gene: evidence for a high frequency of -23T-->A in Japanese subjects.

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10.

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11.

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12.

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13.

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14.

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15.

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16.

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17.

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18.

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19.

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20.

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21.

Heude B et al. (2006) The insulin gene variable number of tandem repeat: associations and interactions with childhood body fat mass and insulin secretion in normal children.

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22.

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23.

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24.

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25.

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26.

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27.

Edghill EL et al. (2008) Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.

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28.

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29.

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30.

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31.

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32.

Lichter P et al. (1990) High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones.

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33.

Soares MB et al. (1985) RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon.

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34.

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35.

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36.

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37.

Elbein SC et al. (1985) Hyperproinsulinemia in a family with a proposed defect in conversion is linked to the insulin gene.

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38.

Williams LG et al. (1985) Allelic variation adjacent to the human insulin and apolipoprotein C-II genes in different ethnic groups.

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39.

Michalova K et al. (1988) Chromosome localization of the human insulin gene in transgenic mouse lines.

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40.

Carroll RJ et al. (1988) A mutant human proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway.

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41.

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42.

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43.

Chan SJ et al. (1987) A mutation in the B chain coding region is associated with impaired proinsulin conversion in a family with hyperproinsulinemia.

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44.

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45.

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46.

Vinik AI et al. (1986) Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

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47.

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48.

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49.

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50.

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51.

Chaganti RS et al. (1985) Germ-line chromosomal localization of genes in chromosome 11p linkage: parathyroid hormone, beta-globin, c-Ha-ras-1, and insulin.

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52.

Todd S et al. (1985) Genes for insulin I and II, parathyroid hormone, and calcitonin are on rat chromosome 1.

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53.

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54.

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55.

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56.

Bell GI et al. (1979) Nucleotide sequence of a cDNA clone encoding human preproinsulin.

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57.

Bell GI et al. (1980) Sequence of the human insulin gene.

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58.

Owerbach D et al. (1980) The insulin gene is located on chromosome 11 in humans.

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59.

Ullrich A et al. (1980) Genetic variation in the human insulin gene.

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60.

Kwok SC et al. (1981) Loss of a restriction endonuclease cleavage site in the gene of a structurally abnormal human insulin.

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61.

Rotwein P et al. (1981) Polymorphism in the 5'-flanking region of the human insulin gene and its possible relation to type 2 diabetes.

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62.

Lebo RV et al. (1982) Assigning the polymorphic human insulin gene to the short arm of chromosome 11 by chromosome sorting.

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63.

Haneda M et al. (1983) Studies on mutant human insulin genes: identification and sequence analysis of a gene encoding [SerB24]insulin.

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64.

Kwok SC et al. (1983) Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (insulin Chicago).

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65.

Shoelson S et al. (1983) Three mutant insulins in man.

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66.

Lebo RV et al. (1983) Recombination within and between the human insulin and beta-globin gene loci.

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67.

Robbins DC et al. (1984) Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion.

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68.

Robbins DC et al. (1984) Biologic and clinical importance of proinsulin.

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69.

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70.

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71.

Shoelson S et al. (1983) Identification of a mutant human insulin predicted to contain a serine-for-phenylalanine substitution.

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72.

Sures I et al. (1980) Nucleotide sequence of human preproinsulin complementary DNA.

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73.

Harper ME et al. (1981) Localization of the human insulin gene to the distal end of the short arm of chromosome 11.

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74.

Robbins DC et al. (1981) A human proinsulin variant at arginine 65.

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75.

Given BD et al. (1980) Diabetes due to secretion of an abnormal insulin.

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76.

Gabbay KH et al. (1980) The insulinopathies.

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77.

Robinson GL et al. (1994) Isolation and characterization of a novel transcription factor that binds to and activates insulin control element-mediated expression.

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78.

Davies PO et al. (1994) Genetic reassignment of the insulin-1 (Ins1) gene to distal mouse chromosome 19.

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79.

Gabbay KH et al. (1976) Familial hyperproinsulinemia. An autosomal dominant defect.

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80.

Deltour L et al. (1993) Differential expression of the two nonallelic proinsulin genes in the developing mouse embryo.

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81.

Hua QX et al. (1993) Paradoxical structure and function in a mutant human insulin associated with diabetes mellitus.

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82.

Röder ME et al. (1996) Hyperproinsulinemia in a three-generation Caucasian family due to mutant proinsulin (Arg65-His) not associated with imparied glucose tolerance: the contribution of mutant proinsulin to insulin bioactivity.

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83.

Yoshioka M et al. (1997) A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant mice.

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84.

Warren-Perry MG et al. (1997) A novel point mutation in the insulin gene giving rise to hyperproinsulinemia.

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85.

Kayo T et al. (1998) Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal period.

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86.

Collinet M et al. (1998) Familial hyperproinsulinaemia due to a mutation substituting histidine for arginine at position 65 in proinsulin: identification of the mutation by restriction enzyme mapping.

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87.

Wang J et al. (1999) A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouse.

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