title: NTNG1 mutations are a rare cause of Rett syndrome.
abstract: A translocation that disrupted the netrin G1 gene (NTNG1) was recently reported in a patient with the early seizure variant of Rett syndrome (RTT). The netrin G1 protein (NTNG1) has an important role in the developing central nervous system, particularly in axonal guidance, signalling and NMDA receptor function and was a good candidate gene for RTT. We recruited 115 patients with RTT (females: 25 classic and 84 atypical; 6 males) but no mutation in the MECP2 gene. For those 52 patients with epileptic seizure onset in the first 6 months of life, CDKL5 mutations were also excluded. We aimed to determine whether mutations in NTNG1 accounted for a significant subset of patients with RTT, particularly those with the early onset seizure variant and other atypical presentations. We sequenced the nine coding exons of NTNG1 and identified four sequence variants, none of which were likely to be pathogenic. Mutations in the NTNG1 gene appear to be a rare cause of RTT but NTNG1 function demands further investigation in relation to the central nervous system pathophysiology of the disorder.
authors.affiliation: Institute of Medical Genetics, Cardiff University, University Hospital of Wales, Cardiff, United Kingdom. archerhl@cardiff.ac.uk
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Archer
authors.forename: Julie C
authors.initials: JC
authors.lastname: Evans
authors.forename: David S
authors.initials: DS
authors.lastname: Millar
authors.forename: Peter W
authors.initials: PW
authors.lastname: Thompson
authors.forename: Alison M
authors.initials: AM
authors.lastname: Kerr
authors.forename: Helen
authors.initials: H
authors.lastname: Leonard
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.forename: David
authors.initials: D
authors.lastname: Ravine
authors.forename: Lazarus
authors.initials: L
authors.lastname: Lazarou
authors.forename: Lucy
authors.initials: L
authors.lastname: Grove
authors.forename: Christopher
authors.initials: C
authors.lastname: Verity
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Whatley
authors.forename: Daniela T
authors.initials: DT
authors.lastname: Pilz
authors.forename: Julian R
authors.initials: JR
authors.lastname: Sampson
authors.forename: Angus J
authors.initials: AJ
authors.lastname: Clarke
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D058851:GPI-Linked Proteins; D005787:Gene Frequency; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000075385:Netrins; D015518:Rett Syndrome / Q000235:genetics*
chemical_list: D058851:GPI-Linked Proteins; D006023:Glycoproteins; C463082:NTNG1 protein, human; D009419:Nerve Tissue Proteins; D000075385:Netrins