title: Dynamic changes in IKBKAP mRNA levels during crisis of familial dysautonomia patients.
abstract: Familial dysautonomia is a neurodegenerative, genetic disorder caused by an autosomal recessive mutation in the IKBKAP gene, which encodes the IkB kinase complex-associated protein. Familial dysautonomia patients have recurrent crises characterized by bouts of nausea, vomiting, hypertension, tachycardia, sweating, blotching and personality changes. The dysautonomia crisis is usually triggered by stressful physiological or emotional events, however the pathophysiology of the crisis is not yet fully clear and little is known about the molecular mechanisms involved in onset and consequences of the crisis.
  
  
  OBJECTIVE
  We have investigated the dysautonomia crisis by evaluating the expression of the familial dysautonomia gene - IKBKAP, in patients during different crisis stages.
  
  
  METHODS
  Baseline IKBKAP mRNA levels in white blood cells were evaluated in thirteen FD patients (fourteen crisis events) and compared to mRNA levels at the onset, during, and after recovery from the crisis.
  
  
  RESULTS
  We have found a significant decrease in IKBKAP mRNA level during the crisis, which is restored to a baseline level after recovery from the crisis.
  
  
  CONCLUSIONS
  We speculate that the familial dysautonomia crisis pathophysiology might be related, at least in part, to the down regulation of the IKBKAP gene. Yet, it is still unclear whether the down regulation in IKBKAP mRNA is caused by the physiological stress events which have triggered the crisis or whether this molecular change is a consequence of the crisis.
authors.affiliation: Israeli Familial Dysautonomia Center, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, The Hebrew University Hadassah Medical School, Jerusalem, Israel; Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Cheishvili
authors.affiliation: Israeli Familial Dysautonomia Center, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, The Hebrew University Hadassah Medical School, Jerusalem, Israel; Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Laiba
authors.affiliation: Israeli Familial Dysautonomia Center, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Rekhtman
authors.affiliation: Israeli Familial Dysautonomia Center, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Claman
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Aharon
authors.initials: A
authors.lastname: Razin
authors.affiliation: Israeli Familial Dysautonomia Center, Department of Pediatrics, Hadassah University Hospital, Mount Scopus, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Channa
authors.initials: C
authors.lastname: Maayan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015984:Causality; D002648:Child; D002675:Child, Preschool; D003289:Convalescence; D015536:Down-Regulation; D004402:Dysautonomia, Familial / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D013312:Stress, Physiological; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C114720:Elp1 protein, human; D012333:RNA, Messenger; D035602:Transcriptional Elongation Factors
keywords: FD crisis; Familial dysautonomia; IKAP; IKBKAP; JNK; Stress; WBC; mRNA