Gliazellen neurotrophischer Faktor
Das GDNF-Gen kodiert einen von Glia-Zellen gebildeten neutrotrophischen Faktor der zusammen mit dem Produkt des RET-Gens die Bildung und Apoptose von Nervenzellen steuert. Mutationen führen zu verschiedenen autosomal dominanten Erkrankungen, dem zentralen Hypoventilationssyndrom, der Hirschsprung-Erkrankung und dem Phäochromozytom.
Gentests:
Klinisch |
Untersuchungsmethoden |
Familienuntersuchung |
Bearbeitungszeit |
5 Tage |
Probentyp |
genomische DNS |
Verknüpfte Erkrankungen:
Referenzen:
1. |
Neel JV et al. (1998) Type II diabetes, essential hypertension, and obesity as "syndromes of impaired genetic homeostasis": the "thrifty genotype" hypothesis enters the 21st century.
|
2. |
None (1962) Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"?
|
3. |
None (2003) Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.
|
4. |
Thornton PS et al. (1998) Familial hyperinsulinism with apparent autosomal dominant inheritance: clinical and genetic differences from the autosomal recessive variant.
|
5. |
Tosi R et al. (1978) Immunological dissection of human Ia molecules.
|
6. |
Duquesnoy RJ et al. (1979) Identification of an HLA-DR-associated system of B-cell alloantigens.
|
7. |
Todd JA et al. (1990) The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese.
|
8. |
Helmuth R et al. (1990) HLA-DQ alpha allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes.
|
9. |
Briata P et al. (1989) Alternative splicing of HLA-DQB transcripts and secretion of HLA-DQ beta-chain proteins: allelic polymorphism in splicing and polyadenylylation sites.
|
10. |
Del Pozzo G et al. (1989) Mummy DNA fragment identified.
|
11. |
Kwok WW et al. (1989) Mutational analysis of the HLA-DQ3.2 insulin-dependent diabetes mellitus susceptibility gene.
|
12. |
Gyllensten UB et al. (1988) Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus.
|
13. |
Todd JA et al. () HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus.
|
14. |
Okada K et al. (1985) Gene organization of DC and DX subregions of the human major histocompatibility complex.
|
15. |
Moriuchi J et al. (1985) Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.
|
16. |
None () Molecular cloning of Ancient Egyptian mummy DNA.
|
17. |
Nadler LM et al. (1981) Monoclonal antibody identifies a new Ia-like (p29,34) polymorphic system linked to the HLA-D/DR region.
|
18. |
None (1981) Role of MHC gene products in immune regulation.
|
19. |
Corte G et al. (1981) Human Ia molecules carrying DC1 determinants differ in both alpha- and beta-subunits from Ia molecules carrying DR determinants.
|
20. |
Sorrentino R et al. (1983) Microfingerprinting analysis of human Ia molecules favours a three loci model.
|
21. |
Cohen D et al. (1984) Class II HLA-DC beta-chain DNA restriction fragments differentiate among HLA-DR2 individuals in insulin-dependent diabetes and multiple sclerosis.
|
22. |
Schenning L et al. (1984) Both alpha and beta chains of HLA-DC class II histocompatibility antigens display extensive polymorphism in their amino-terminal domains.
|
23. |
Bono MR et al. (1982) Direct evidence of homology between human DC-1 antigen and murine I-A molecules.
|
24. |
Hsu SH et al. (1981) Genetic control of major histocompatibility complex-linked immune responses to synthetic polypeptides in man.
|
25. |
Auffray C et al. (1982) cDNA clone for the heavy chain of the human B cell alloantigen DC1: strong sequence homology to the HLA-DR heavy chain.
|
26. |
Tanigaki N et al. (1980) Molecular identification of human Ia antigens coded for by a gene locus closely linked to HLA-DR locus.
|
27. |
Accolla RS et al. (1981) Distinct forms of both alpha and beta subunits are present in the human Ia molecular pool.
|
28. |
Shackelford DA et al. (1981) Human B-cell alloantigens DC1, MT1, and LB12 are identical to each other but distinct from the HLA-DR antigen.
|
29. |
Meyer CG et al. (1994) HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection.
|
30. |
Suzuki Y et al. (1996) Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients.
|
31. |
Nabozny GH et. al. (1996) HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis.
|
32. |
Bradley DS et. al. (1997) HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis.
|
33. |
Ferber KM et al. (1999) Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes.
|
34. |
Wen L et al. (2000) In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes.
|
35. |
Lambert NC et al. (2000) Cutting edge: persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity.
|
36. |
Cucca F et al. (2001) A correlation between the relative predisposition of MHC class II alleles to type 1 diabetes and the structure of their proteins.
|
37. |
Kim CY et al. (2004) Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease.
|
38. |
Hovhannisyan Z et al. (2008) The role of HLA-DQ8 beta57 polymorphism in the anti-gluten T-cell response in coeliac disease.
|
39. |
Stanescu HC et al. (2011) Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.
|
40. |
Cao H et al. (2000) Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy.
|
41. |
Shackleton S et al. (2000) LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.
|
42. |
Speckman RA et al. (2000) Mutational and haplotype analyses of families with familial partial lipodystrophy (Dunnigan variety) reveal recurrent missense mutations in the globular C-terminal domain of lamin A/C.
|
43. |
Garg A et al. (2001) Phenotypic heterogeneity in patients with familial partial lipodystrophy (dunnigan variety) related to the site of missense mutations in lamin a/c gene.
|
44. |
Schmidt HH et al. (2001) Dyslipemia in familial partial lipodystrophy caused by an R482W mutation in the LMNA gene.
|
45. |
Vigouroux C et al. (2001) Nuclear envelope disorganization in fibroblasts from lipodystrophic patients with heterozygous R482Q/W mutations in the lamin A/C gene.
|
46. |
Caux F et al. (2003) A new clinical condition linked to a novel mutation in lamins A and C with generalized lipoatrophy, insulin-resistant diabetes, disseminated leukomelanodermic papules, liver steatosis, and cardiomyopathy.
|
47. |
Vigouroux C et al. (2003) LMNA mutations in atypical Werner's syndrome.
|
48. |
Lanktree M et al. (2007) Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660).
|
49. |
Njølstad PR et al. (2001) Neonatal diabetes mellitus due to complete glucokinase deficiency.
|
50. |
Köbberling J et al. (1975) Lipodystrophy of the extremities. A dominantly inherited syndrome associated with lipatrophic diabetes.
|
51. |
Davidson MB et al. (1975) Metabolic studies in familial partial lipodystrophy of the lower trunk and extremities.
|
52. |
Stoffel M et al. (1992) Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.
|
53. |
Hattersley AT et al. (1992) Linkage of type 2 diabetes to the glucokinase gene.
|
54. |
Velho G et al. (1992) Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young.
|
55. |
Katagiri H et al. (1992) Nonsense mutation of glucokinase gene in late-onset non-insulin-dependent diabetes mellitus.
|
56. |
Permutt MA et al. (1992) Glucokinase and NIDDM. A candidate gene that paid off.
|
57. |
Stoffel M et al. (1992) Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus.
|
58. |
Froguel P et al. (1992) Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus.
|
59. |
Vionnet N et al. (1992) Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus.
|
60. |
Matsutani A et al. (1992) A polymorphic (CA)n repeat element maps the human glucokinase gene (GCK) to chromosome 7p.
|
61. |
Mishra SK et al. (1992) A 2-cM genetic linkage map of human chromosome 7p that includes 47 loci.
|
62. |
Tanizawa Y et al. (1991) Human liver glucokinase gene: cloning and sequence determination of two alternatively spliced cDNAs.
|
63. |
None (1990) Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes.
|
64. |
Reardon W et al. (1990) Partial lipodystrophy syndromes--a further male case.
|
65. |
None (1988) Banting lecture 1988. Role of insulin resistance in human disease.
|
66. |
Burn J et al. (1986) Partial lipoatrophy with insulin resistant diabetes and hyperlipidaemia (Dunnigan syndrome).
|
67. |
Köbberling J et al. (1986) Familial partial lipodystrophy: two types of an X linked dominant syndrome, lethal in the hemizygous state.
|
68. |
Dunnigan MG et al. (1974) Familial lipoatrophic diabetes with dominant transmission. A new syndrome.
|
69. |
Greene ML et al. (1970) Benign symmetric lipomatosis (Launois-Bensaude adenolipomatosis) with gout and hyperlipoproteinemia.
|
70. |
Wettke-Schäfer R et al. (1983) X-linked dominant inherited diseases with lethality in hemizygous males.
|
71. |
Robbins DC et al. (1982) Familial partial lipodystrophy: complications of obesity in the non-obese?
|
72. |
Grupe A et al. (1995) Transgenic knockouts reveal a critical requirement for pancreatic beta cell glucokinase in maintaining glucose homeostasis.
|
73. |
Rowe RE et al. (1995) Linkage and association between insulin-dependent diabetes mellitus (IDDM) susceptibility and markers near the glucokinase gene on chromosome 7.
|
74. |
Bali D et al. (1995) Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene.
|
75. |
Froguel P et al. (1993) Non-sense mutation of glucokinase gene.
|
76. |
Chiu KC et al. (1993) Non-sense mutation of glucokinase gene.
|
77. |
Byrne MM et al. (1994) Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations.
|
78. |
Matschinsky F et al. (1993) Glucokinase as pancreatic beta cell glucose sensor and diabetes gene.
|
79. |
Sun F et al. (1993) Deletion of the donor splice site of intron 4 in the glucokinase gene causes maturity-onset diabetes of the young.
|
80. |
None (1993) Glucokinase and candidate genes for type 2 (non-insulin-dependent) diabetes mellitus.
|
81. |
Froguel P et al. (1993) Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus.
|
82. |
Stoffel M et al. (1993) Identification of glucokinase mutations in subjects with gestational diabetes mellitus.
|
83. |
Stone LM et al. (1996) A variation at position -30 of the beta-cell glucokinase gene promoter is associated with reduced beta-cell function in middle-aged Japanese-American men.
|
84. |
Heimberg H et al. (1996) The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.
|
85. |
Velho G et al. (1996) Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2) subjects.
|
86. |
Aizawa T et al. (1996) Analysis of the pancreatic beta cell in the mouse with targeted disruption of the pancreatic beta cell-specific glucokinase gene.
|
87. |
Velho G et al. (1997) Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families.
|
88. |
Jackson SN et al. (1997) Dunnigan-Kobberling syndrome: an autosomal dominant form of partial lipodystrophy.
|
89. |
Glaser B et al. (1998) Familial hyperinsulinism caused by an activating glucokinase mutation.
|
90. |
Peters JM et al. (1998) Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21-22.
|
91. |
Dunger DB et al. (1998) Association of the INS VNTR with size at birth. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.
|
92. |
None (1998) Weighing in on diabetes risk.
|
93. |
Hattersley AT et al. (1998) Mutations in the glucokinase gene of the fetus result in reduced birth weight.
|
94. |
Jackson SN et al. (1998) A defect in the regional deposition of adipose tissue (partial lipodystrophy) is encoded by a gene at chromosome 1q.
|
95. |
Garg A et al. (1999) Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety).
|
96. |
Anderson JL et al. (1999) Confirmation of linkage of hereditary partial lipodystrophy to chromosome 1q21-22.
|
97. |
None (2000) Gender differences in the prevalence of metabolic complications in familial partial lipodystrophy (Dunnigan variety).
|
98. |
None (2001) Premature atherosclerosis associated with monogenic insulin resistance.
|
99. |
Christesen HB et al. (2002) The second activating glucokinase mutation (A456V): implications for glucose homeostasis and diabetes therapy.
|
100. |
Datta SR et al. (2002) Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis.
|
101. |
Grimsby J et al. (2003) Allosteric activators of glucokinase: potential role in diabetes therapy.
|
102. |
Danial NN et al. (2003) BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis.
|
103. |
Gloyn AL et al. (2003) Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations.
|
104. |
None (2004) Acquired and inherited lipodystrophies.
|
105. |
Inoue M et al. (2004) A series of maturity onset diabetes of the young, type 2 (MODY2) mouse models generated by a large-scale ENU mutagenesis program.
|
106. |
März W et al. (2004) G(-30)A polymorphism in the pancreatic promoter of the glucokinase gene associated with angiographic coronary artery disease and type 2 diabetes mellitus.
|
107. |
Cuesta-Muñoz AL et al. (2004) Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation.
|
108. |
Johansen A et al. (2005) Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.
|
109. |
Vits L et al. (2006) Identification of novel and recurrent glucokinase mutations in Belgian and Luxembourg maturity onset diabetes of the young patients.
|
110. |
Terauchi Y et al. (2007) Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance.
|
111. |
Pinterova D et al. (2007) Six novel mutations in the GCK gene in MODY patients.
|
112. |
Spuler S et al. (2007) Muscle and nerve pathology in Dunnigan familial partial lipodystrophy.
|
113. |
Vantyghem MC et al. (2008) Fertility and obstetrical complications in women with LMNA-related familial partial lipodystrophy.
|
114. |
Araújo-Vilar D et al. (2009) Site-dependent differences in both prelamin A and adipogenic genes in subcutaneous adipose tissue of patients with type 2 familial partial lipodystrophy.
|
115. |
Kassem S et al. (2010) Large islets, beta-cell proliferation, and a glucokinase mutation.
|
116. |
None (1946) Lipodystrophy and hepatomegaly, with diabetes, lipaemia, and other metabolic disturbances; a case throwing new light on the action of insulin.
|
117. |
Shen Y et al. (2011) Insight into the biochemical characteristics of a novel glucokinase gene mutation.
|
118. |
Hofmeister-Brix A et al. (2013) Identification of the ubiquitin-like domain of midnolin as a new glucokinase interaction partner.
|
119. |
Wagner AJ et al. (1992) Expression, regulation, and chromosomal localization of the Max gene.
|
120. |
Gilladoga AD et al. (1992) Mapping of MAX to human chromosome 14 and mouse chromosome 12 by in situ hybridization.
|
121. |
Prendergast GC et al. (1991) Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation.
|
122. |
Blackwood EM et al. (1991) Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc.
|
123. |
Zervos AS et al. (1995) Mxi2, a mitogen-activated protein kinase that recognizes and phosphorylates Max protein.
|
124. |
Schindelhauer D et al. (1995) The gene coding for glial cell line derived neurotrophic factor (GDNF) maps to chromosome 5p12-p13.1.
|
125. |
Hopewell R et al. (1995) The nerve growth factor-responsive PC12 cell line does not express the Myc dimerization partner Max.
|
126. |
Tomac A et al. (1995) Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo.
|
127. |
Beck KD et al. (1995) Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain.
|
128. |
Oppenheim RW et al. (1995) Developing motor neurons rescued from programmed and axotomy-induced cell death by GDNF.
|
129. |
Schaar DG et al. (1993) Regional and cell-specific expression of GDNF in rat brain.
|
130. |
Lin LF et al. (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.
|
131. |
Bermingham N et al. (1995) Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5.
|
132. |
Gash DM et al. (1996) Functional recovery in parkinsonian monkeys treated with GDNF.
|
133. |
Durbec P et al. (1996) GDNF signalling through the Ret receptor tyrosine kinase.
|
134. |
Sánchez MP et al. (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF.
|
135. |
Pichel JG et al. (1996) Defects in enteric innervation and kidney development in mice lacking GDNF.
|
136. |
Moore MW et al. (1996) Renal and neuronal abnormalities in mice lacking GDNF.
|
137. |
Treanor JJ et al. (1996) Characterization of a multicomponent receptor for GDNF.
|
138. |
Grandori C et al. (1996) Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo.
|
139. |
Angrist M et al. (1996) Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient.
|
140. |
Salomon R et al. (1996) Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease.
|
141. |
Ivanchuk SM et al. (1996) De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease.
|
142. |
Woodward ER et al. (1997) Genetic predisposition to phaeochromocytoma: analysis of candidate genes GDNF, RET and VHL.
|
143. |
Pichel JG et al. (1996) GDNF is required for kidney development and enteric innervation.
|
144. |
Hofstra RM et al. () Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype.
|
145. |
Amiel J et al. (1998) Mutations of the RET-GDNF signaling pathway in Ondine's curse.
|
146. |
Nguyen QT et al. (1998) Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle.
|
147. |
Ramer MS et al. (2000) Functional regeneration of sensory axons into the adult spinal cord.
|
148. |
Meng X et al. (2000) Regulation of cell fate decision of undifferentiated spermatogonia by GDNF.
|
149. |
Messer CJ et al. (2000) Role for GDNF in biochemical and behavioral adaptations to drugs of abuse.
|
150. |
Martucciello G et al. (2000) Pathogenesis of Hirschsprung's disease.
|
151. |
Boucher TJ et al. (2000) Potent analgesic effects of GDNF in neuropathic pain states.
|
152. |
Kordower JH et al. (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease.
|
153. |
Bahuau M et al. (2001) GDNF as a candidate modifier in a type 1 neurofibromatosis (NF1) enteric phenotype.
|
154. |
Wang CY et al. (2001) Ca(2+) binding protein frequenin mediates GDNF-induced potentiation of Ca(2+) channels and transmitter release.
|
155. |
Shen L et al. (2002) Gdnf haploinsufficiency causes Hirschsprung-like intestinal obstruction and early-onset lethality in mice.
|
156. |
Eketjäll S et al. (2002) Functional characterization of mutations in the GDNF gene of patients with Hirschsprung disease.
|
157. |
Japón MA et al. (2002) Glial-derived neurotropic factor and RET gene expression in normal human anterior pituitary cell types and in pituitary tumors.
|
158. |
Borghini S et al. (2002) Hirschsprung associated GDNF mutations do not prevent RET activation.
|
159. |
Nair SK et al. (2003) X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors.
|
160. |
Amiel J et al. (2003) Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome.
|
161. |
Gill SS et al. (2003) Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease.
|
162. |
Iwashita T et al. (2003) Hirschsprung disease is linked to defects in neural crest stem cell function.
|
163. |
Lawrence JM et al. (2004) Transplantation of Schwann cell line clones secreting GDNF or BDNF into the retinas of dystrophic Royal College of Surgeons rats.
|
164. |
Dahia PL et al. (2005) Novel pheochromocytoma susceptibility loci identified by integrative genomics.
|
165. |
Anitha M et al. (2006) GDNF rescues hyperglycemia-induced diabetic enteric neuropathy through activation of the PI3K/Akt pathway.
|
166. |
Carnicella S et al. (2008) GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse.
|
167. |
Qin Y et al. (2010) Germline mutations in TMEM127 confer susceptibility to pheochromocytoma.
|
168. |
Comino-Méndez I et al. (2011) Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma.
|
169. |
NCBI article
NCBI 2668
|
170. |
OMIM.ORG article
Omim 600837
|
171. |
Orphanet article
Orphanet ID 122076
|
Update: 14. August 2020