title: [Charcot-Marie-Tooth disorders with autosomal recessive inheritance. Search for the molecular diagnostics model].
abstract: THE AIM was focused on molecular analysis of the selected genes associated with autosomal recessive Charcot-Marie-Tooth neuropathies (AR-CMT) and construction of a molecular diagnostic algorithm in this group of disorders in the Polish population.
  
  
  METHODS
  We analyzed a group of 138 subjects from 62 families with probably autosomal recessive inheritance and the control group of 52 individuals. The studies covered molecular genetic analysis of PMP22 gene dosage (real-time polymerase chain reaction and polymerase chain reaction restriction fragments length polymorphisms), analysis of coding regions of the GDAP1, PRX, EGR2 and CTDP1 genes using: mutation screening (single strand conformation polymorphism and heteroduplex analysis), sequencing and bioinformatics approach to the gene sequence variants.
  
  
  RESULTS
  Thirty sequence variants have been found in the analysed genes, 5 pathogenic mutations in the GDAP1 gene and 2 pathogenic mutations in the PRX gene. On the basis of bioinformatic analysis other nucleotide changes have been categorized as harmless polymorphisms and variants of unknown pathogenic effect.
  
  
  CONCLUSIONS
  This is the first study focused on the autosomal recessive Charcot-Marie-Tooth disease in the Polish population. Our results show the difficulties in the interpretation of the pathogenic effect of the sequence variants (pathogenic mutation or polymorphism) which is essential for molecular diagnostics in CMT disease.
authors.affiliation: Zespół Chorób Nerwowo-Mieśniowych Instytutu Medycyny Doświadczalnej i Klinicznej im. M.J. Mossakowskiego Polskiej Akademii Nauk, ul. A. Pawińskiego 5, 02-106 Warszawa.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Kabzińska
authors.forename: Maria
authors.initials: M
authors.lastname: Franaszczyk
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kochański
mesh_terms: D000465:Algorithms; D016022:Case-Control Studies; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length
chemical_list: C118663:GDAP protein; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C086745:periaxin