Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel

Pankreasagenesie 2

Die Pankreasagenesie 2 ist eine autosomal rezessive Erkrankung, die durch Mutationen des PTF1A-Gens hervorgerufen wird. In den bislang publizierten Fällen zeigte sich auch eine Agenesie des Kleinhirns und die Betroffenen waren nicht lebensfähig.

Gliederung

Pankreopriver Diabetes mellitus
Mitchell-Riley-Syndrom
Pankreasaganesie mit Herzfehlern
Pankreasagenesie 1
Pankreasagenesie 2
PTF1A

Referenzen:

1.

Odievre M et al. (1975) [Fructose 1,6-diphosphatase deficiency in 2 sisters].

[^]
2.

Moses SW et al. (1991) Fructose-1,6-diphosphatase deficiency in Israel.

[^]
3.

Bührdel P et al. (1990) Biochemical and clinical observations in four patients with fructose-1,6-diphosphatase deficiency.

[^]
4.

Baker L et al. (1970) Fasting hypoglycaemia and metabolic acidosis associated with deficiency of hepatic fructose-1,6-diphosphatase activity.

[^]
5.

Sia CL et al. (1969) Studies on the subunit structure of rabbit liver fructose diphosphatase.

[^]
6.

Melancon SB et al. (1972) Detection of fructose-6,-diphosphatase deficiency with use of white blood cells.

[^]
7.

Baerlocher K et al. (1971) Infantile lactic acidosis due to hereditary fructose 1,6-diphosphatase deficiency.

[^]
8.

Pagliara AS et al. (1972) Hepatic fructose-1,6-diphosphatase deficiency. A cause of lactic acidosis and hypoglycemia in infancy.

[^]
9.

Greene HL et al. (1972) "Ketotic hypoglycemia" due to hepatic fructose-1,6-diphosphatase deficiency: treatment with folic acid.

[^]
10.

el-Maghrabi MR et al. (1995) Human fructose-1,6-bisphosphatase gene (FBP1): exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency.

[^]
11.

Kikawa Y et al. (1995) Identification of a genetic mutation in a family with fructose-1,6- bisphosphatase deficiency.

[^]
12.

Besley GT et al. (1994) Fructose-1,6-bisphosphatase deficiency: severe phenotype with normal leukocyte enzyme activity.

[^]
13.

Rothschild CB et al. (1995) Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus.

[^]
14.

Kikawa Y et al. (1997) Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency.

[^]
15.

Tillmann H et al. (1998) Isolation and characterization of an allelic cDNA for human muscle fructose-1,6-bisphosphatase.

[^]
16.

Berge KE et al. (2000) Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters.

[^]
17.

Lee MH et al. (2001) Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption.

[^]
18.

Lu K et al. (2001) Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively.

[^]
19.

Repa JJ et al. (2002) Regulation of ATP-binding cassette sterol transporters ABCG5 and ABCG8 by the liver X receptors alpha and beta.

[^]
20.

Lu K et al. (2002) Molecular cloning, genomic organization, genetic variations, and characterization of murine sterolin genes Abcg5 and Abcg8.

[^]
21.

Matsuura T et al. (2002) Two newly identified genomic mutations in a Japanese female patient with fructose-1,6-bisphosphatase (FBPase) deficiency.

[^]
22.

Yu L et al. (2002) Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion.

[^]
23.

Sehayek E et al. (2002) Loci on chromosomes 14 and 2, distinct from ABCG5/ABCG8, regulate plasma plant sterol levels in a C57BL/6J x CASA/Rk intercross.

[^]
24.

None (2003) Role of ABC transporters in secretion of cholesterol from liver into bile.

[^]
25.

Yang C et al. (2004) Disruption of cholesterol homeostasis by plant sterols.

[^]
26.

Rees DC et al. (2005) Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia.

[^]
27.

Mannucci L et al. (2007) Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene.

[^]
28.

Rios J et al. (2010) Identification by whole-genome resequencing of gene defect responsible for severe hypercholesterolemia.

[^]
29.

Li B et al. (2014) Fructose-1,6-bisphosphatase opposes renal carcinoma progression.

[^]
30.

Tosi R et al. (1978) Immunological dissection of human Ia molecules.

[^]
31.

Duquesnoy RJ et al. (1979) Identification of an HLA-DR-associated system of B-cell alloantigens.

[^]
32.

Todd JA et al. (1990) The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese.

[^]
33.

Helmuth R et al. (1990) HLA-DQ alpha allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes.

[^]
34.

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.

[^]
35.

Del Pozzo G et al. (1989) Mummy DNA fragment identified.

[^]
36.

Kwok WW et al. (1989) Mutational analysis of the HLA-DQ3.2 insulin-dependent diabetes mellitus susceptibility gene.

[^]
37.

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.

[^]
38.

Todd JA et al. () HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus.

[^]
39.

Okada K et al. (1985) Gene organization of DC and DX subregions of the human major histocompatibility complex.

[^]
40.

Moriuchi J et al. (1985) Nucleotide sequence of an HLA-DQ alpha chain derived from a DRw9 cell line: genetic and evolutionary implications.

[^]
41.

None () Molecular cloning of Ancient Egyptian mummy DNA.

[^]
42.

Nadler LM et al. (1981) Monoclonal antibody identifies a new Ia-like (p29,34) polymorphic system linked to the HLA-D/DR region.

[^]
43.

None (1981) Role of MHC gene products in immune regulation.

[^]
44.

Corte G et al. (1981) Human Ia molecules carrying DC1 determinants differ in both alpha- and beta-subunits from Ia molecules carrying DR determinants.

[^]
45.

Sorrentino R et al. (1983) Microfingerprinting analysis of human Ia molecules favours a three loci model.

[^]
46.

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.

[^]
47.

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.

[^]
48.

Bono MR et al. (1982) Direct evidence of homology between human DC-1 antigen and murine I-A molecules.

[^]
49.

Hsu SH et al. (1981) Genetic control of major histocompatibility complex-linked immune responses to synthetic polypeptides in man.

[^]
50.

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.

[^]
51.

Tanigaki N et al. (1980) Molecular identification of human Ia antigens coded for by a gene locus closely linked to HLA-DR locus.

[^]
52.

Accolla RS et al. (1981) Distinct forms of both alpha and beta subunits are present in the human Ia molecular pool.

[^]
53.

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.

[^]
54.

Meyer CG et al. (1994) HLA-D alleles associated with generalized disease, localized disease, and putative immunity in Onchocerca volvulus infection.

[^]
55.

Suzuki Y et al. (1996) Evidence for genetic regulation of susceptibility to toxoplasmic encephalitis in AIDS patients.

[^]
56.

Nabozny GH et. al. (1996) HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis.

[^]
57.

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.

[^]
58.

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.

[^]
59.

Wen L et al. (2000) In vivo evidence for the contribution of human histocompatibility leukocyte antigen (HLA)-DQ molecules to the development of diabetes.

[^]
60.

Lambert NC et al. (2000) Cutting edge: persistent fetal microchimerism in T lymphocytes is associated with HLA-DQA1*0501: implications in autoimmunity.

[^]
61.

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.

[^]
62.

Kim CY et al. (2004) Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease.

[^]
63.

Hovhannisyan Z et al. (2008) The role of HLA-DQ8 beta57 polymorphism in the anti-gluten T-cell response in coeliac disease.

[^]
64.

Stanescu HC et al. (2011) Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy.

[^]
65.

Chong JX et al. (2012) A population-based study of autosomal-recessive disease-causing mutations in a founder population.

[^]
66.

Paulus JM et al. (1978) Platelet formation in Mediterranean macrothrombocytosis.

[^]
67.

None (1975) Mediterranean macrothrombocytopenia.

[^]
68.

Shulman RS et al. (1976) Beta-sitosterolemia and xanthomatosis.

[^]
69.

Hatanaka I et al. (1990) Spinal cord compression with paraplegia in xanthomatosis due to normocholesterolemic sitosterolemia.

[^]
70.

Nguyen LB et al. (1990) A molecular defect in hepatic cholesterol biosynthesis in sitosterolemia with xanthomatosis.

[^]
71.

Beaty TH et al. (1986) Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia.

[^]
72.

Salen G et al. (1985) Increased plasma cholestanol and 5 alpha-saturated plant sterol derivatives in subjects with sitosterolemia and xanthomatosis.

[^]
73.

Skrede B et al. (1985) The presence of 5 alpha-sitostanol in the serum of a patient with phytosterolemia, and its biosynthesis from plant steroids in rats with bile fistula.

[^]
74.

Bhattacharyya AK et al. (1974) Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters.

[^]
75.

Ducrou W et al. (1969) Stomatocytes, haemolytic anaemia and abdominal pain in Mediterranean migrants. Some examples of a new syndrome?

[^]
76.

Kwiterovich PO et al. (1981) Hyperapobetalipoproteinaemia in two families with xanthomas and phytosterolaemia.

[^]
77.

Brahimi S et al. (1984) Platelet count and mean platelet volume in an Algerian population indicating a low prevalence of Mediterranean macrothrombocytopenia.

[^]
78.

None (1980) Phytosterolaemia, xanthomatosis and premature atherosclerotic arterial disease: a case with high plant sterol absorption, impaired sterol elimination and low cholesterol synthesis.

[^]
79.

Wang C et al. (1981) A unique patient with coexisting cerebrotendinous xanthomatosis and beta-sitosterolemia.

[^]
80.

Salen G et al. (1996) Abnormal cholesterol biosynthesis in sitosterolaemia and the Smith-Lemli-Opitz syndrome.

[^]
81.

Patel SB et al. (1998) Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21.

[^]
82.

Savoia A et al. (2001) Autosomal dominant macrothrombocytopenia in Italy is most frequently a type of heterozygous Bernard-Soulier syndrome.

[^]
83.

Lu K et al. (2001) High-resolution physical and transcript map of human chromosome 2p21 containing the sitosterolaemia locus.

[^]
84.

Lee MH et al. (2001) Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities.

[^]
85.

None (2003) Images in clinical medicine. Phytosterolemia and xanthomatosis.

[^]
86.

Solcà C et al. (2005) Sitosterolaemia in Switzerland: molecular genetics links the US Amish-Mennonites to their European roots.

[^]
87.

Stewart GW et al. (2006) Mediterranean stomatocytosis/macrothrombocytopenia: update from Adelaide, Australia.

[^]
88.

Buch S et al. (2007) A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.

[^]
89.

Stewart GW et al. (2008) Mediterranean macrothrombocytopenia and phytosterolaemia/sitosterolaemia.

[^]
90.

van den Ouweland JM et al. (1992) Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness.

[^]
91.

Ballinger SW et al. (1992) Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion.

[^]
92.

Reardon W et al. (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA.

[^]
93.

Alcolado JC et al. (1991) Importance of maternal history of non-insulin dependent diabetic patients.

[^]
94.

Sue CM et al. (1993) Mitochondrial gene mutations and diabetes mellitus.

[^]
95.

Ballinger SW et al. (1994) Mitochondrial diabetes revisited.

[^]
96.

Schulz JB et al. (1993) Mitochondrial gene mutations and diabetes mellitus.

[^]
97.

Velho G et al. (1996) Clinical phenotypes, insulin secretion, and insulin sensitivity in kindreds with maternally inherited diabetes and deafness due to mitochondrial tRNALeu(UUR) gene mutation.

[^]
98.

't Hart LM et al. (1996) Heteroplasmy levels of a mitochondrial gene mutation associated with diabetes mellitus decrease in leucocyte DNA upon aging.

[^]
99.

Vialettes BH et al. (1997) Phenotypic expression of diabetes secondary to a T14709C mutation of mitochondrial DNA. Comparison with MIDD syndrome (A3243G mutation): a case report.

[^]
100.

Kameoka K et al. (1998) Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes.

[^]
101.

Martin Negrier ML et al. (1998) Partial triplication of mtDNA in maternally transmitted diabetes mellitus and deafness.

[^]
102.

Chinnery PF et al. (1999) Nonrandom tissue distribution of mutant mtDNA.

[^]
103.

Guillausseau PJ et al. (2001) Maternally inherited diabetes and deafness: a multicenter study.

[^]
104.

None (2001) Mitochondrial DNA mutations and diabetes: another step toward individualized medicine.

[^]
105.

Ogun O et al. (2012) Pearls & oy-sters: maternally inherited diabetes and deafness presenting with ptosis and macular pattern dystrophy.

[^]
106.

Wright NM et al. (1993) Permanent neonatal diabetes mellitus and pancreatic exocrine insufficiency resulting from congenital pancreatic agenesis.

[^]
107.

Stoffers DA et al. (1997) Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence.

[^]
108.

Schwitzgebel VM et al. (2003) Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1.

[^]
109.

Maitra M et al. (2010) Identification of GATA6 sequence variants in patients with congenital heart defects.

[^]
110.

Lin X et al. (2010) A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect.

[^]
111.

Kodo K et al. (2009) GATA6 mutations cause human cardiac outflow tract defects by disrupting semaphorin-plexin signaling.

[^]
112.

Yorifuji T et al. (1994) Hereditary pancreatic hypoplasia, diabetes mellitus, and congenital heart disease: a new syndrome?

[^]
113.

Krapp A et al. (1996) The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix protein.

[^]
114.

Suzuki E et al. (1996) The human GATA-6 gene: structure, chromosomal location, and regulation of expression by tissue-specific and mitogen-responsive signals.

[^]
115.

Morrisey EE et al. (1998) GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo.

[^]
116.

Krapp A et al. (1998) The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreas.

[^]
117.

Hoveyda N et al. (1999) Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome.

[^]
118.

Adell T et al. (2000) Role of the basic helix-loop-helix transcription factor p48 in the differentiation phenotype of exocrine pancreas cancer cells.

[^]
119.

Laitinen MP et al. (2000) Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors.

[^]
120.

Rose SD et al. (2001) The role of PTF1-P48 in pancreatic acinar gene expression.

[^]
121.

Kawaguchi Y et al. (2002) The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors.

[^]
122.

Ketola I et al. (2003) Transcription factor GATA-6, cell proliferation, apoptosis, and apoptosis-related proteins Bcl-2 and Bax in human fetal testis.

[^]
123.

Sellick GS et al. (2003) A novel gene for neonatal diabetes maps to chromosome 10p12.1-p13.

[^]
124.

Sellick GS et al. (2004) Mutations in PTF1A cause pancreatic and cerebellar agenesis.

[^]
125.

Ho CK et al. (2005) Increased transcription and increased messenger ribonucleic acid (mRNA) stability contribute to increased GATA6 mRNA abundance in polycystic ovary syndrome theca cells.

[^]
126.

Lepore JJ et al. (2006) GATA-6 regulates semaphorin 3C and is required in cardiac neural crest for cardiovascular morphogenesis.

[^]
127.

Xin M et al. (2006) A threshold of GATA4 and GATA6 expression is required for cardiovascular development.

[^]
128.

Kamnasaran D et al. (2007) GATA6 is an astrocytoma tumor suppressor gene identified by gene trapping of mouse glioma model.

[^]
129.

Masui T et al. (2007) Early pancreatic development requires the vertebrate Suppressor of Hairless (RBPJ) in the PTF1 bHLH complex.

[^]
130.

Al-Shammari M et al. (2011) A novel PTF1A mutation in a patient with severe pancreatic and cerebellar involvement.

[^]
131.

Yorifuji T et al. (2012) Dominantly inherited diabetes mellitus caused by GATA6 haploinsufficiency: variable intrafamilial presentation.

[^]
132.

Weedon MN et al. (2014) Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis.

[^]
133.

Yu L et al. (2014) Whole exome sequencing identifies de novo mutations in GATA6 associated with congenital diaphragmatic hernia.

[^]
134.

Rosas M et al. (2014) The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal.

[^]
135.

Lemons JA et al. (1979) Congenital absence of the pancreas and intrauterine growth retardation.

[^]
136.

Méhes K et al. (1976) Agenesis of pancreas and gall-bladder in an infant of incest.

[^]
137.

Winter WE et al. (1986) Congenital pancreatic hypoplasia: a syndrome of exocrine and endocrine pancreatic insufficiency.

[^]
138.

Dourov N et al. () [Agenesia of the pancreas. Anatomo-clinical observations of a case of diabetes mellitus, with steatorrhea and hypotrophy, in a newborn infant].

[^]
139.

Howard CP et al. (1980) Long-term survival in a case of functional pancreatic agenesis.

[^]
140.

Widness JA et al. (1982) Permanent neonatal diabetes in an infant of an insulin-dependent mother.

[^]
141.

Wildling R et al. (1993) Agenesis of the dorsal pancreas in a woman with diabetes mellitus and in both of her sons.

[^]
142.

Stoffers DA et al. (1997) Early-onset type-II diabetes mellitus (MODY4) linked to IPF1.

[^]
143.

Thomas IH et al. (2009) Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation.

[^]
144.

Nicolino M et al. (2010) A novel hypomorphic PDX1 mutation responsible for permanent neonatal diabetes with subclinical exocrine deficiency.

[^]
145.

Fajans SS et al. (2010) Obesity and hyperinsulinemia in a family with pancreatic agenesis and MODY caused by the IPF1 mutation Pro63fsX60.

[^]
146.

OMIM.ORG article

Omim 615935 [^]
Update: 10. Mai 2019