title: Submicroscopic subtelomeric aberrations in Chinese patients with unexplained developmental delay/mental retardation.
abstract: BACKGROUND
  Subtelomeric imbalance is widely accepted as related to developmental delay/mental retardation (DD/MR). Fine mapping of aberrations in gene-enriched subtelomeric regions provides essential clues for localizing critical regions, and provides a strategy for identifying new candidate genes. To date, no large-scale study has been conducted on subtelomeric aberrations in DD/MR patients in mainland China.
  
  
  METHODS
  This study included 451 Chinese children with moderate to severe clinically unexplained DD/MR. The subtelomere-MLPA (multiplex ligation dependent probe amplification) and Affymetrix human SNP array 6.0 were used to determine the subtelomeric copy number variations. The exact size and the breakpoint of each identified aberration were well defined.
  
  
  RESULTS
  The submicroscopic subtelomeric aberrations were identified in 23 patients, with a detection rate of 5.1%. 16 patients had simple deletions, 2 had simple duplications and 5 with both deletions and duplications. The deletions involved 14 different subtelomeric regions (1p, 2p, 4p, 6p, 7p, 7q, 8p, 9p, 10p, 11q, 14q, 15q, 16p and 22q), and duplications involved 7 subtelomeric regions (3q, 4p, 6q, 7p, 8p, 12p and 22q). Of all the subtelomeric aberrations found in Chinese subjects, the most common was 4p16.3 deletion. The sizes of the deletions varied from 0.6 Mb to 12 Mb, with 5-143 genes inside. Duplicated regions were 0.26 Mb to 11 Mb, with 6-202 genes inside. In this study, four deleted subtelomeric regions and one duplicated region were smaller than any other previously reported, specifically the deletions in 11q25, 8p23.3, 7q36.3, 14q32.33, and the duplication in 22q13. Candidate genes inside each region were proposed.
  
  
  CONCLUSIONS
  Submicroscopic subtelomeric aberrations were detected in 5.1% of Chinese children with clinically unexplained DD/MR. Four deleted subtelomeric regions and one duplicated region found in this study were smaller than any previously reported, which will be helpful for further defining the candidate dosage sensitive gene associated with DD/MR.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Taoyun
authors.initials: T
authors.lastname: Ji
authors.forename: Jingmin
authors.initials: J
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Huifang
authors.initials: H
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Gao
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.forename: Liwen
authors.initials: L
authors.lastname: Wang
authors.forename: Zhongshu
authors.initials: Z
authors.lastname: Zhou
authors.forename: Lili
authors.initials: L
authors.lastname: Tian
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Zhong
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.forename: Xiru
authors.initials: X
authors.lastname: Wu
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D016254:Mutagenesis, Insertional; D021141:Nucleic Acid Amplification Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure*; D055815:Young Adult
references.citation: Am J Med Genet C Semin Med Genet. 2003 Feb 15;117C(1):3-14
references.pmid: 12561053
references.citation: Ann N Y Acad Sci. 2009 Jan;1151:157-66
references.pmid: 19154522
references.citation: Hum Mutat. 2005 Nov;26(5):477-86
references.pmid: 16170807
references.citation: Curr Opin Genet Dev. 2008 Jun;18(3):241-50
references.pmid: 18694825
references.citation: Hum Genet. 2002 May;110(5):439-43
references.pmid: 12073014
references.citation: Curr Opin Neurol. 2008 Apr;21(2):117-22
references.pmid: 18317267
references.citation: Eur J Med Genet. 2006 Nov-Dec;49(6):505-10
references.pmid: 16905374
references.citation: Am J Hum Genet. 2003 Dec;73(6):1261-70
references.pmid: 14628292
references.citation: Eur J Hum Genet. 2009 Oct;17(10):1347-53
references.pmid: 19384346
references.citation: Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4913-7
references.pmid: 1594593
references.citation: Am J Med Genet A. 2009 May;149A(5):1012-8
references.pmid: 19365838
references.citation: J Biol Chem. 2008 Oct 24;283(43):29586-92
references.pmid: 18718915
references.citation: J Med Genet. 2002 Sep;39(9):e53
references.pmid: 12205123
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Sep 5;141B(6):584-90
references.pmid: 16823807
references.citation: Hum Mutat. 2004 Jan;23(1):17-21
references.pmid: 14695528
references.citation: Nat Genet. 1995 Feb;9(2):132-40
references.pmid: 7719339
references.citation: Pediatr Clin North Am. 2008 Oct;55(5):1071-84, xi
references.pmid: 18929052
references.citation: Am J Med Genet C Semin Med Genet. 2003 Feb 15;117C(1):15-24
references.pmid: 12561054
references.citation: Genet Med. 2005 Nov-Dec;7(9):650-4
references.pmid: 16301868
references.citation: Am J Hum Genet. 2005 Oct;77(4):606-16
references.pmid: 16175506
references.citation: Am J Med Genet A. 2005 Oct 15;138A(3):218-24
references.pmid: 16152642
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):421-4
references.pmid: 18615476
references.citation: Am J Med Genet A. 2007 Jul 1;143A(13):1431-41
references.pmid: 17568414
references.citation: Am J Med Genet. 2000 Jan 3;90(1):60-8
references.pmid: 10602119
references.citation: Orphanet J Rare Dis. 2008 May 27;3:14
references.pmid: 18505557
references.citation: Clin Genet. 2002 Oct;62(4):315-20
references.pmid: 12372060
references.citation: Am J Med Genet C Semin Med Genet. 2007 Nov 15;145C(4):393-8
references.pmid: 17926345
references.citation: Am J Med Genet. 1996 Mar 1;62(1):77-83
references.pmid: 8779331
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1101-8
references.pmid: 18361433
references.citation: Am J Med Genet A. 2008 Sep 1;146A(17):2242-51
references.pmid: 18663743
references.citation: Pediatrics. 2006 Jun;117(6):2304-16
references.pmid: 16740881
references.citation: Am J Med Genet A. 2008 Oct 1;146A(19):2449-54
references.pmid: 18792974
references.citation: Eur J Med Genet. 2005 Oct-Dec;48(4):388-96
references.pmid: 16378923
references.citation: Nat Med. 2001 Apr;7(4):497-501
references.pmid: 11283680
references.citation: Am J Hum Genet. 2008 Feb;82(2):477-88
references.pmid: 18252227
references.citation: Ment Retard Dev Disabil Res Rev. 2002;8(3):117-34
references.pmid: 12216056
references.citation: J Med Genet. 2001 Mar;38(3):145-50
references.pmid: 11238680
references.citation: Clin Genet. 2007 Oct;72(4):362-8
references.pmid: 17850634
references.citation: J Genet Hum. 1988 Dec;36(5):425-46
references.pmid: 2975324
references.citation: Hum Mutat. 2007 Oct;28(10):958-67
references.pmid: 17492636
references.citation: Am J Med Genet A. 2004 Aug 15;129A(1):51-61
references.pmid: 15266616
references.citation: Isr Med Assoc J. 2008 Nov;10(11):821-6
references.pmid: 19070297
references.citation: Am J Med Genet A. 2004 Jan 1;124A(1):10-8
references.pmid: 14679581
references.citation: Am J Med Genet A. 2006 Nov 1;140(21):2324-9
references.pmid: 17022077
references.citation: J Med Genet. 2005 Apr;42(4):299-306
references.pmid: 15805155
references.citation: Lancet. 1999 Nov 13;354(9191):1676-81
references.pmid: 10568569
references.citation: Am J Med Genet A. 2008 Jul 1;146A(13):1754-60
references.pmid: 18546282
references.citation: Neurogenetics. 2009 Apr;10(2):89-95
references.pmid: 18855024
references.citation: Nat Genet. 2007 Jan;39(1):25-7
references.pmid: 17173049
references.citation: J Med Genet. 2003 Aug;40(8):575-84
references.pmid: 12920066
references.citation: Am J Med Genet. 2001 Apr 1;99(4):314-9
references.pmid: 11251999
references.citation: Am J Med Genet A. 2006 Jan 15;140(2):144-50
references.pmid: 16353244
references.citation: J Med Genet. 2004 Apr;41(4):241-8
references.pmid: 15060094