Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

MODY12 Diabetes

MODY12 ist ein autosomal dominanter einsetzender Typ 2 Diabetes, der sich aufgrund einer Mutation im Gen ABCC8 entwickelt. In der pathogenese kommt es zuerst zu einer überschießenden Insulinsekretion was später zu einer Erschöpfung der beta-Zelle und damit zur Entwicklung eines Diabetes führt.

Klinischer Befund

Mit seinem milderen klinischen Verlauf ähnelt der MODY Typ 12 eher dem MODY2. Im Unterschied zu diesem entwickelt er sich aber aus einer anfänglichen Insulinhypersekretion.

Gliederung

MODY Diabetes
MODY1 Diabetes
MODY10 Diabetes
MODY11 Diabetes
MODY12 Diabetes
ABCC8
MODY13 Diabetes
MODY14 Diabetes
MODY2 Diabetes
MODY3 Diabetes
MODY4 Diabetes
MODY5 Diabetes
MODY6 Diabetes
MODY7 Diabetes
MODY8 Diabetes
MODY9 Diabetes

Referenzen:

1.

Thornton PS et. al. (1998) Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.

[^]
2.

Otonkoski T et. al. (1999) A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland.

[^]
3.

Glaser B et. al. (1999) Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.

[^]
4.

Huopio H et. al. (2000) Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.

[^]
5.

Huopio H et. al. (2003) A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1.

[^]
6.

Thornton PS et. al. (2003) Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.

[^]
7.

Magge SN et. al. (2004) Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.

[^]
8.

Tornovsky S et. al. (2004) Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.

[^]
9.

Proks P et al. (2006) A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes.

[^]
10.

Babenko AP et al. (2006) Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.

[^]
11.

Ellard S et. al. (2007) Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.

[^]
12.

Thomas PM et. al. (1995) Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.

[^]
13.

Thomas PM et. al. (1996) Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy.

[^]
14.

Nestorowicz A et. al. (1996) Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews.

[^]
15.

Dunne MJ et. al. (1997) Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor.

[^]
16.

Verkarre V et. al. (1998) Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.

[^]
17.

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.

[^]
18.

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.

[^]
19.

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

[^]
20.

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

[^]
21.

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.

[^]
22.

Lohmueller KE et. al. (2003) Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease.

[^]
23.

Glaser B et. al. (1999) Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene.

[^]
24.

Giurgea I et. al. (2006) The Knudson's two-hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism.

[^]
25.

Thomas PM et. al. (1995) Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy.

[^]
26.

Fantes JA et. al. (1995) A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.

[^]
27.

Glaser B et. al. (1994) Familial hyperinsulinism maps to chromosome 11p14-15.1, 30 cM centromeric to the insulin gene.

[^]
28.

Philipson LH et. al. (1995) Pas de deux or more: the sulfonylurea receptor and K+ channels.

[^]
29.

Aguilar-Bryan L et. al. (1995) Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.

[^]
30.

Inoue H et. al. (1996) Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians.

[^]
31.

Gribble FM et. al. (1997) The essential role of the Walker A motifs of SUR1 in K-ATP channel activation by Mg-ADP and diazoxide.

[^]
32.

Nestorowicz A et. al. (1998) Genetic heterogeneity in familial hyperinsulinism.

[^]
33.

Goksel DL et. al. (1998) Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.

[^]
34.

Ryan F et. al. (1998) Hyperinsulinism: molecular aetiology of focal disease.

[^]
35.

Matsuo M et. al. (2000) Functional analysis of a mutant sulfonylurea receptor, SUR1-R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy.

[^]
36.

Reis AF et. al. (2000) Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians.

[^]
37.

Meirhaeghe A et. al. (2001) Impact of sulfonylurea receptor 1 genetic variability on non-insulin-dependent diabetes mellitus prevalence and treatment: a population study.

[^]
38.

Pocai A et. al. (2005) Hypothalamic K(ATP) channels control hepatic glucose production.

[^]
39.

Simard JM et. al. (2006) Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.

[^]
40.

de Wet H et. al. (2007) Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.

[^]
41.

Banerjee I et. al. (2011) The contribution of rapid KATP channel gene mutation analysis to the clinical management of children with congenital hyperinsulinism.

[^]
42.

Flanagan S et. al. (2012) Partial ABCC8 gene deletion mutations causing diazoxide-unresponsive hyperinsulinaemic hypoglycaemia.

[^]
43.

Flanagan SE et. al. (2013) Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.

[^]