RGD Reference Report - NKX2.5 mutations in patients with tetralogy of fallot. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

NKX2.5 mutations in patients with tetralogy of fallot.

Authors: Goldmuntz, E  Geiger, E  Benson, DW 
Citation: Goldmuntz E, etal., Circulation. 2001 Nov 20;104(21):2565-8.
RGD ID: 1581133
Pubmed: PMID:11714651   (View Abstract at PubMed)

BACKGROUND: Recent reports have implicated mutations in the transcription factor NKX2.5 as a cause of tetralogy of Fallot (TOF). To estimate the frequency of NKX2.5 mutations in TOF patients and to further investigate the genotype-phenotype correlation of NKX2.5 mutations, we genotyped 114 TOF patients. METHODS AND RESULTS: Patients were recruited prospectively (November 1992 through June 1999) and tested for a 22q11 deletion; those with 22q11 deletion or recognized chromosomal alteration were excluded from the present study. Patients were screened for NKX2.5 alterations by conformation-sensitive gel electrophoresis and sequencing of fragments with aberrant mobility. Four heterozygous mutations were identified in 6 unrelated patients with cases of TOF, including 3 with pulmonary atresia and 5 with right aortic arch; none had ECG evidence of PR interval prolongation. Three of 4 mutations (Glu21Gln, Arg216Cys, and Ala219Val) altered highly conserved amino acids, of which 2 mapped in the conserved NK2 domain. The fourth mutation (Arg25Cys) was identified in 3 unrelated probands in the present study and has been previously reported. No homeodomain mutations were identified. CONCLUSIONS: NKX2.5 mutations are the first gene defects identified in nonsyndromic TOF patients. NKX2.5 mutation is present in >/=4% of TOF patients. Mutations identified in the present study mapped outside of the homeodomain, were not associated with atrioventricular conduction disturbances, and were not fully penetrant, in contrast to mutations previously reported that impair homeodomain function.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NKX2-5Humantetralogy of Fallot  IAGP DNA:missense mutations:cds:multiple (human)RGD 
Nkx2-5Rattetralogy of Fallot  ISONKX2-5 (Homo sapiens)DNA:missense mutations:cds:multiple (human)RGD 
Nkx2-5Mousetetralogy of Fallot  ISONKX2-5 (Homo sapiens)DNA:missense mutations:cds:multiple (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NKX2-5HumanAbnormal pulmonary valve morphology  IAGP DNA:missense mutations:cds:multipleRGD 
NKX2-5HumanRight aortic arch  IAGP DNA:missense mutations:cds:multipleRGD 
NKX2-5HumanRight ventricular hypertrophy  IAGP DNA:missense mutations:cds:multipleRGD 
NKX2-5HumanVentricular septal defect  IAGP DNA:missense mutations:cds:multipleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nkx2-5  (NK2 homeobox 5)

Genes (Mus musculus)
Nkx2-5  (NK2 homeobox 5)

Genes (Homo sapiens)
NKX2-5  (NK2 homeobox 5)


Additional Information