title: Copy number changes and methylation patterns in an isodicentric and a ring chromosome of 15q11-q13: report of two cases and review of literature.
abstract: BACKGROUND
  The low copy repeats (LCRs) in chromosome 15q11-q13 have been recognized as breakpoints (BP) for not only intrachromosomal deletions and duplications but also small supernumerary marker chromosomes 15, sSMC(15)s, in the forms of isodicentric chromosome or small ring chromosome. Further characterization of copy number changes and methylation patterns in these sSMC(15)s could lead to better understanding of their phenotypic consequences.
  
  
  METHODS
  Routine G-band karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay were performed on two Chinese patients with a sSMC(15).
  
  
  RESULTS
  Patient 1 showed an isodicentric 15, idic(15)(q13), containing symmetrically two copies of a 7.7 Mb segment of the 15q11-q13 region by a BP3::BP3 fusion. Patient 2 showed a ring chromosome 15, r(15)(q13), with alternative one-copy and two-copy segments spanning a 12.3 Mb region. The defined methylation pattern indicated that the idic(15)(q13) and the r(15)(q13) were maternally derived.
  
  
  CONCLUSIONS
  Results from these two cases and other reported cases from literature indicated that combined karyotyping, aCGH and MS-MLPA analyses are effective to define the copy number changes and methylation patterns for sSMC(15)s in a clinical setting. The characterized genomic structure and epigenetic pattern of sSMC(15)s could lead to further gene expression profiling for better phenotype correlation.
authors.affiliation: Shenzhen Maternity and Child Healthcare Hospital, 3012 Fuqiang Road, Shenzhen, Guangdong China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Shenzhen Maternity and Child Healthcare Hospital, 3012 Fuqiang Road, Shenzhen, Guangdong China ; Department of Genetics, Yale School of Medicine, New Haven, CT USA.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wu
authors.affiliation: Shenzhen Maternity and Child Healthcare Hospital, 3012 Fuqiang Road, Shenzhen, Guangdong China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Shenzhen Maternity and Child Healthcare Hospital, 3012 Fuqiang Road, Shenzhen, Guangdong China.
authors.forename: Fuwei
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT USA ; First Affiliated Hospital, Biomedical Translational Research Institute, Jinan University, Guangzhou, Guangdong China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT USA.
authors.forename: Peining
authors.initials: P
authors.lastname: Li
authors.affiliation: Shenzhen Maternity and Child Healthcare Hospital, 3012 Fuqiang Road, Shenzhen, Guangdong China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Xie
keywords: 15q11-q13; Array comparative genomic hybridization (aCGH); Isodicentric chromosome; Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA); Ring chromosome