title: Recurrent benign copy number variants & issues in interpretation of variants of unknown significance identified by cytogenetic microarray in Indian patients with intellectual disability.
abstract: OBJECTIVE
  Cytogenetic microarray (CMA) is now recommended as a first-tier clinical diagnostic test in cases with idiopathic intellectual disability and/or developmental delay (ID/DD). Along with clinically relevant variants, CMA platforms also identify variants of unknown significance (VUS). This study was done to look for utility and various issues in interpretation of copy number variants (CNVs) in Indian patients with ID/DD.
  
  
  METHODS
  The CMA was performed in 86 Indian patients with idiopathic ID/DD with or without dysmorphic features. CNV was reported if copy number gain was >400 kb in size and copy number loss was > 200 kb in size.
  
  
  RESULTS
  Pathogenic CNVs were found in 18 of 86 (20.9%) patients. One large (14 Mb size) de novo heterozygous copy number gain was found in one patient. VUS (total 31) were present in 17 of 86 (19.7%) patients. Five novel recurrent benign CNVs were also present in our patients.
  
  
  CONCLUSIONS
  Our findings highlight the difficulties in interpretation of CNVs identified by CMA. More Indian data on VUS and recurrent benign CNVs will be helpful in the interpretation of CMA in patients with ID/DD.
authors.forename: Vijay Raju
authors.initials: VR
authors.lastname: Boggula
authors.forename: Meenal
authors.initials: M
authors.lastname: Agarwal
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kumar
authors.forename: Shally
authors.initials: S
authors.lastname: Awasthi
authors.affiliation: Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Shubha R
authors.initials: SR
authors.lastname: Phadke
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012008:Recurrence
references.citation: Nature. 2006 Nov 23;444(7118):444-54
references.pmid: 17122850
references.citation: J Med Genet. 2009 Feb;46(2):123-31
references.pmid: 19015223
references.citation: Am J Hum Genet. 2010 May 14;86(5):749-64
references.pmid: 20466091
references.citation: Hum Mol Genet. 2010 Oct 15;19(R2):R176-87
references.pmid: 20807775
references.citation: Genet Med. 2010 Nov;12(11):742-5
references.pmid: 20962661
references.citation: Prenat Diagn. 2011 Mar;31(3):235-43
references.pmid: 21374637
references.citation: Genet Med. 2011 Jul;13(7):680-5
references.pmid: 21681106
references.citation: Clin Lab Med. 2011 Dec;31(4):565-80, viii
references.pmid: 22118737
references.citation: Genet Med. 2012 Feb;14(2):250-8
references.pmid: 22241091
references.citation: N Engl J Med. 2012 Oct 4;367(14):1321-31
references.pmid: 22970919
references.citation: Genet Med. 2013 Jan;15(1):70-8
references.pmid: 22858719
references.citation: Indian J Med Res. 2014 Jan;139(1):66-75
references.pmid: 24604040
references.citation: Hum Mutat. 2012 Jun;33(6):930-40
references.pmid: 26285306