title: TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability.
abstract: BACKGROUND
  TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49).
  
  
  RESULTS
  We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events.
  
  
  CONCLUSIONS
  We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin.
authors.affiliation: Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel; The Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Med. Ctr., Israel. Electronic address: galih.md@gmail.com.
authors.forename: Gali
authors.initials: G
authors.lastname: Heimer
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Danit
authors.initials: D
authors.lastname: Oz-Levi
authors.affiliation: Cancer Research Center, Pediatric Hemato/Oncology Unit, Edmond and Lily Safra Children's, Hospital, The Chaim Sheba Med. Ctr., Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Eyal
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University, Med. Ctr., Jerusalem, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Edvardson
authors.affiliation: Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel; The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel.
authors.forename: Andreea
authors.initials: A
authors.lastname: Nissenkorn
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Ruzzo
authors.affiliation: Pediatric Sleep clinic, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Szeinberg
authors.affiliation: Familial Dysautonomia Centre, Pediatric Department, Hadassah Hospital, Hebrew University Hadassah, Medical School, Jerusalem, Israel.
authors.forename: Channa
authors.initials: C
authors.lastname: Maayan
authors.affiliation: Pulmonary Institute, Schneider Children's Med. Ctr., Sackler Faculty of Medicine, Tel Aviv University, Israel.
authors.forename: Meir
authors.initials: M
authors.lastname: Mai-Zahav
authors.affiliation: The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel; Pediatric Pulmonary Unit, The Edmond and Lily Safra Children's Hospital, Sheba Med. Ctr., Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Efrati
authors.affiliation: The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel; Danek Gertner Institute of Human Genetics, Sheba Med. Ctr., Ramat Gan, Israel.
authors.forename: Elon
authors.initials: E
authors.lastname: Pras
authors.affiliation: Danek Gertner Institute of Human Genetics, Sheba Med. Ctr., Ramat Gan, Israel.
authors.forename: Haike
authors.initials: H
authors.lastname: Reznik-Wolf
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Lancet
authors.affiliation: Institute for Genomic Medicine, Columbia University Medical School, Columbia University Med. Ctr., New York, NY 10032, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.affiliation: The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel; Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
authors.affiliation: Genetic Institute, Ha'Emek Med. Ctr., Afula 18101, Israel; Rappaport Faculty of Medicine, Technion, Israel.
authors.forename: Stavit A
authors.initials: SA
authors.lastname: Shalev
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University, Med. Ctr., Jerusalem, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
authors.affiliation: Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel; The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel. Electronic address: bruria.benzeev@sheba.health.gov.il.
authors.forename: Bruria
authors.initials: B
authors.lastname: Ben Zeev
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D002675:Child, Preschool; D019295:Computational Biology; D004247:DNA / Q000235:genetics; D004402:Dysautonomia, Familial / Q000235:genetics*; D004568:Electrodiagnosis; D059472:Exome; D016368:Frameshift Mutation / Q000235:genetics; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000523:psychology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics* / Q000523:psychology; D007585:Jews; D008297:Male; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D009460:Neurologic Examination; D010375:Pedigree; D012120:Respiration Disorders / Q000209:etiology / Q000235:genetics; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000523:psychology
chemical_list: D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C578280:TECPR2 protein, human; D004247:DNA
keywords: Autophagy; HSAN III; Hereditary spastic paraparesis; IKBKAP; Jewish Ashkenazi; TECPR2