Abstract
BackgroundThe 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.MethodsRoutine 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).ResultsPatient 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.ConclusionsResults 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.
Highlights
The low copy repeats (LCRs) in chromosome 15q11-q13 have been recognized as breakpoints (BP) for intrachromosomal deletions and duplications and small supernumerary marker chromosomes 15, sSMC(15)s, in the forms of isodicentric chromosome or small ring chromosome
The low copy repeats (LCRs) clustered in the chromosome 15q11-q13 region are known breakpoints 1 to 5 (BP1-5) for meiotic non-allelic homologous recombination which results in interstitial deletions and duplications [1]
The small sSMC(15)s have breakpoints at the BP1 or BP2 proximal to the critical region and usually clinically irrelevant, while the large sSMC(15)s frequently extend beyond the BP3 to include the critical region and are frequently associated with abnormal phenotypes [5,6,7,8,9,10,11,12,13,14,15,16,17]
Summary
The low copy repeats (LCRs) in chromosome 15q11-q13 have been recognized as breakpoints (BP) for intrachromosomal deletions and duplications and small supernumerary marker chromosomes 15, sSMC(15)s, in the forms of isodicentric chromosome or small ring chromosome. The low copy repeats (LCRs) clustered in the chromosome 15q11-q13 region are known breakpoints 1 to 5 (BP1-5) for meiotic non-allelic homologous recombination which results in interstitial deletions and duplications [1]. Deletions of this region account for approximately 70 % of patients with Prader-Willi syndrome (PWS, OMIM#176270) and Angelman syndrome (AS, OMIM#105830). Results from a large case series showed that about 60 % percent mosaic sSMC cases with clinical abnormalities had no direct correlation to the level of mosaicism in the peripheral blood and there is no simple relationship between clinical abnormalities and sSMC mosaicism [4]
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