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.
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: C Fauth; H Zhang; S Harabacz; J Brown; K Saracoglu; G Lederer; O Rittinger; I Rost; R Eils; L Kearney; M R Speicher Journal: Hum Genet Date: 2001-11-09 Impact factor: 4.132
Authors: Patrick J Bernier; Andreanne Bedard; Jonathan Vinet; Martin Levesque; Andre Parent Journal: Proc Natl Acad Sci U S A Date: 2002-08-12 Impact factor: 11.205
Authors: A J Dawson; S Putnam; J Schultz; D Riordan; C Prasad; C R Greenberg; B N Chodirker; A A Mhanni; A E Chudley Journal: Clin Genet Date: 2002-12 Impact factor: 4.438
Authors: Helger G Yntema; Francis A Poppelaars; Esther Derksen; Astrid R Oudakker; Tanja van Roosmalen; Anja Jacobs; Hanneke Obbema; Han G Brunner; Ben C J Hamel; Hans van Bokhoven Journal: Am J Med Genet Date: 2002-07-01
Authors: Hyung-Goo Kim; Hyun-Taek Kim; Natalia T Leach; Fei Lan; Reinhard Ullmann; Asli Silahtaroglu; Ingo Kurth; Anja Nowka; Ihn Sik Seong; Yiping Shen; Michael E Talkowski; Douglas Ruderfer; Ji-Hyun Lee; Caron Glotzbach; Kyungsoo Ha; Susanne Kjaergaard; Alex V Levin; Bernd F Romeike; Tjitske Kleefstra; Oliver Bartsch; Sarah H Elsea; Ethylin Wang Jabs; Marcy E MacDonald; David J Harris; Bradley J Quade; Hans-Hilger Ropers; Lisa G Shaffer; Kerstin Kutsche; Lawrence C Layman; Niels Tommerup; Vera M Kalscheuer; Yang Shi; Cynthia C Morton; Cheol-Hee Kim; James F Gusella Journal: Am J Hum Genet Date: 2012-07-05 Impact factor: 11.025
Authors: Eric Deneault; Muhammad Faheem; Sean H White; Deivid C Rodrigues; Song Sun; Wei Wei; Alina Piekna; Tadeo Thompson; Jennifer L Howe; Leon Chalil; Vickie Kwan; Susan Walker; Peter Pasceri; Frederick P Roth; Ryan Kc Yuen; Karun K Singh; James Ellis; Stephen W Scherer Journal: Elife Date: 2019-02-12 Impact factor: 8.140
Authors: Milena Simioni; François Artiguenave; Vincent Meyer; Ilária C Sgardioli; Nilma L Viguetti-Campos; Isabella Lopes Monlleó; Andréa T Maciel-Guerra; Carlos E Steiner; Vera L Gil-da-Silva-Lopes Journal: Mol Syndromol Date: 2017-06-01
Authors: Yan Xiong; Fengling Li; Nicolas Babault; Hong Wu; Aiping Dong; Hong Zeng; Xin Chen; Cheryl H Arrowsmith; Peter J Brown; Jing Liu; Masoud Vedadi; Jian Jin Journal: Bioorg Med Chem Date: 2017-06-19 Impact factor: 3.641