title: Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome.
abstract: BACKGROUND
  A new syndrome has been recognised following thorough analysis of patients with a terminal submicroscopic subtelomeric deletion of chromosome 9q. These have in common severe mental retardation, hypotonia, brachycephaly, flat face with hypertelorism, synophrys, anteverted nares, thickened lower lip, carp mouth with macroglossia, and conotruncal heart defects. The minimum critical region responsible for this 9q subtelomeric deletion syndrome (9q-) is approximately 1.2 Mb and encompasses at least 14 genes.
  
  
  OBJECTIVE
  To characterise the breakpoints of a de novo balanced translocation t(X;9)(p11.23;q34.3) in a mentally retarded female patient with clinical features similar to the 9q- syndrome.
  
  
  RESULTS
  Sequence analysis of the break points showed that the translocation was fully balanced and only one gene on chromosome 9 was disrupted--Euchromatin Histone Methyl Transferase1 (Eu-HMTase1)--encoding a histone H3 lysine 9 methyltransferase (H3-K9 HMTase). This indicates that haploinsufficiency of Eu-HMTase1 is responsible for the 9q submicroscopic subtelomeric deletion syndrome. This observation was further supported by the spatio-temporal expression of the gene. Using tissue in situ hybridisation studies in mouse embryos and adult brain, Eu-HMTase1 was shown to be expressed in the developing nervous system and in specific peripheral tissues. While expression is selectively downregulated in adult brain, substantial expression is retained in the olfactory bulb, anterior/ventral lateral ventricular wall, and hippocampus and weakly in the piriform cortex.
  
  
  CONCLUSIONS
  The expression pattern of this gene suggests a role in the CNS development and function, which is in line with the severe mental retardation and behaviour problems in patients who lack one copy of the gene.
authors.affiliation: Department of Human Genetics, University Medical Centre St Radboud, Nijmegen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Kleefstra
authors.forename: M
authors.initials: M
authors.lastname: Smidt
authors.forename: M J G
authors.initials: MJ
authors.lastname: Banning
authors.forename: A R
authors.initials: AR
authors.lastname: Oudakker
authors.forename: H
authors.initials: H
authors.lastname: Van Esch
authors.forename: A P M
authors.initials: AP
authors.lastname: de Brouwer
authors.forename: W
authors.initials: W
authors.lastname: Nillesen
authors.forename: E A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: B C J
authors.initials: BC
authors.lastname: Hamel
authors.forename: D
authors.initials: D
authors.lastname: de Bruijn
authors.forename: J-P
authors.initials: JP
authors.lastname: Fryns
authors.forename: H G
authors.initials: HG
authors.lastname: Yntema
authors.forename: H G
authors.initials: HG
authors.lastname: Brunner
authors.forename: B B A
authors.initials: BB
authors.lastname: de Vries
authors.forename: H
authors.initials: H
authors.lastname: van Bokhoven
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D013577:Syndrome; D016615:Telomere / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C455847:EHMT1 protein, human; D008780:Methyltransferases; D011495:Histone-Lysine N-Methyltransferase