Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics

Nicolien M. Hanemaaijer, Birgit Sikkema-Raddatz, Gerben van der Vries, Trijnie Dijkhuizen, Roel Hordijk, Anthonie J. van Essen, Hermine E. Veenstra-Knol, Wilhelmina S. Kerstjens-Frederikse, Johanna C. Herkert, Erica H. Gerkes, Lamberta K. Leegte, Klaas Kok, Richard J. Sinke, Conny M. A. van Ravenswaaij-Arts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Scopus)

Abstract

The correct interpretation of copy number gains in patients with developmental delay and multiple congenital anomalies is hampered by the large number of copy number variations (CNVs) encountered in healthy individuals. The variable phenotype associated with copy number gains makes interpretation even more difficult. Literature shows that inheritence, size and presence in healthy individuals are commonly used to decide whether a certain copy number gain is pathogenic, but no general consensus has been established. We aimed to develop guidelines for interpreting gains detected by array analysis using array CGH data of 300 patients analysed with the 105K Agilent oligo array in a diagnostic setting. We evaluated the guidelines in a second, independent, cohort of 300 patients. In the first 300 patients 797 gains of four or more adjacent oligonucleotides were observed. Of these, 45.4% were de novo and 54.6% were familial. In total, 94.8% of all de novo gains and 87.1% of all familial gains were concluded to be benign CNVs. Clinically relevant gains ranged from 288 to 7912 kb in size, and were significantly larger than benign gains and gains of unknown clinical relevance (P

Original languageEnglish
Pages (from-to)161-165
Number of pages5
JournalEuropean Journal of Human Genetics
Volume20
Issue number2
DOIs
Publication statusPublished - Feb-2012

Keywords

  • genome-wide array analysis
  • copy number gain
  • microduplication
  • guideline
  • MENTAL-RETARDATION
  • DEVELOPMENTAL DELAY
  • CLINICAL-PRACTICE
  • HUMAN GENOME
  • MICRODUPLICATIONS
  • ABNORMALITIES
  • DUPLICATION
  • CHALLENGES
  • PHENOTYPES
  • WORKFLOW

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