title: Mutated nup62 causes autosomal recessive infantile bilateral striatal necrosis.
abstract: OBJECTIVE
  The objective of this study was to identify the gene causing autosomal recessive infantile bilateral striatal necrosis.
  
  
  METHODS
  We have mapped the disease gene in the candidate region to approximately 230kb on 19q13.33 in 8 interrelated families including a total of 12 patients and 39 unaffected individuals.
  
  
  RESULTS
  Sequencing of the nup62 gene showed a missense mutation causing a change from glutamine to proline (Q391P) in all the patients, producing a substitution from a polar, hydrophilic residue to a nonpolar, neutral residue. All the other 12 candidate genes were sequenced, and no pathogenic sequence changes were found. Comparisons of p62 protein sequences from diverse species indicate that glutamine at position 391 is highly conserved. Five prenatal diagnoses were performed in three at-risk families.
  
  
  CONCLUSIONS
  This is the second example of a nuclear pore complex protein causing mendelian disease in humans (the first one is triple A syndrome). Our findings suggest that p62 has a cell type-specific role and is important in the degeneration of the basal ganglia in humans.
authors.affiliation: Department of Medical Genetics, Schneider Children's Medical Center of Israel and Rabin Medical Center, Petah Tikva, Israel. basel@post.tau.ac.il
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Liora
authors.initials: L
authors.lastname: Muncher
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.forename: Michal
authors.initials: M
authors.lastname: Yahav
authors.forename: Limor
authors.initials: L
authors.lastname: Rainshtein
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
authors.forename: Nurit
authors.initials: N
authors.lastname: Magal
authors.forename: Ellen
authors.initials: E
authors.lastname: Taub
authors.forename: Valerie
authors.initials: V
authors.lastname: Drasinover
authors.forename: Hanna
authors.initials: H
authors.lastname: Shalev
authors.forename: Revital
authors.initials: R
authors.lastname: Attia
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: Amos J
authors.initials: AJ
authors.lastname: Simon
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
mesh_terms: D000328:Adult; D018912:Arabs; D015153:Blotting, Western; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D019295:Computational Biology; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005455:Fluorescent Antibody Technique; D007839:Functional Laterality / Q000502:physiology; D008040:Genetic Linkage; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009154:Mutation / Q000502:physiology*; D009336:Necrosis; D017072:Neostriatum / Q000473:pathology*; D028861:Nuclear Pore Complex Proteins; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D008562:Membrane Glycoproteins; D028861:Nuclear Pore Complex Proteins; C049312:nuclear pore protein p62; D004247:DNA