Tetrasomy 9p Mosaicism Associated with a Normal Phenotype in Two Cases

Papoulidis, Ioannis; Kontodiou, Maria; Tzimina, Maria; Saitis, I; Hamid, AB; Klein, Elisabeth; Kosyakova, Nadezda; Kordaß, Ulrike; Kunz, Jürgen; Siomou, Elisa; Nicolaides, P; Orrù, Sandro; Thomaidis, Loretta; Liehr, Thomas; Mb, Petersen; Manolakos, Emmanouil

doi:10.1159/000337520

Cited by 18 publications

(22 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mosaic chromosomal aneuploidies have also been reported in other autosomes in both phenotypically normal and abnormal individuals. Examples include partial tetrasomy on chromosome 5 and 9 and mosaic trisomies of chromosome 13 55–60 .…”

Section: The Spectrum Of Genetic Mosaicismmentioning

confidence: 99%

Detectable Clonal Mosaicism in the Human Genome

Machiela

Chanock

2013

Seminars in Hematology

View full text Add to dashboard Cite

Human genetic mosaicism is the presence of two or more cellular populations with distinct genotypes in an individual who developed from a single fertilized ovum. While initially observed across a spectrum of rare genetic disorders, detailed assessment of data from genome-wide association studies now reveal that detectable clonal mosaicism involving large structural alterations (> 2 Mb) can also be seen in populations of apparently healthy individuals. The first generation of descriptive studies have generated new interest in understanding the molecular basis of the affected genomic regions, percent of the cellular subpopulation involved, and developmental timing of the underlying mutational event, which could reveal new insights into the initiation, clonal expansion and phenotypic manifestations of mosaic events. Early evidence indicates detectable clonal mosaicism increases in frequency with age and could preferentially occur in males. The observed pattern of recurrent events affecting specific chromosomal regions indicates some regions are more susceptible to these events, which could reflect inter-individual differences in genomic stability. Moreover, it is also plausible that the presence of large structural events could be associated with cancer risk. The characterization of detectable genetic mosaicism reveals that there could be important dynamic changes in the human genome associated with the aging process, which could be associated with risk for common disorders, such as cancer, cardiovascular disease, diabetes, and neurological disorders.

show abstract

Section: The Spectrum Of Genetic Mosaicismmentioning

confidence: 99%

Detectable Clonal Mosaicism in the Human Genome

Machiela

Chanock

2013

Seminars in Hematology

View full text Add to dashboard Cite

show abstract

“…However, normal phenotypes are also possible. [6][7][8] This report identifies, for the first time to our knowledge, mosaic tetrasomy of 9p as predisposing to the development of IM, which is associated with an upregulation of type I IFN activity.…”

Section: Discussionmentioning

confidence: 62%

Mosaic Tetrasomy 9p: A Mendelian Condition Associated With Pediatric-Onset Overlap Myositis

et al. 2015

View full text Add to dashboard Cite

Pediatric-onset inflammatory myositis (IM) and systemic lupus erythematosus (SLE) are rare inflammatory diseases. Both result from the complex interaction of genetic and environmental factors. An increasing number of Mendelian conditions predisposing to the development of SLE have been recently identified. These include monogenic conditions, referred to as the type I interferonopathies, associated with a primary upregulation of type I interferon (IFN), a key cytokine in the pathogenesis of SLE and some cases of IM. Here, we report on a pediatric-onset inflammatory overlap phenotype in a 6-year-old girl who was shown to carry mosaic tetrasomy 9p. The patient presented with myositis overlapping with lupuslike features. Myositis was characterized by a proximal muscular weakness and HLA class I antigen myofiber overexpression on muscle biopsy. Lupus-like manifestations consisted of pericarditis, pleuritis, and positive antinuclear and anti-SSA (Sjögren-syndrome A) antibodies. Complete remission was achieved with corticosteroids and mycophenolate mofetyl. Analysis of tetrasomy 9p showed mosaic tetrasomy in the 9p24.3q12 region, including the type I IFN cluster, and increased expression of IFN-stimulated genes. These data suggest that mosaic tetrasomy 9p can be associated with an upregulation of type I IFN signaling, predisposing to inflammatory myositis and lupus-like features. Thus, unexplained muscle or other organ involvement in patients carrying mosaic tetrasomy of the type IFN cluster of chromosome 9p should lead to the search for IM and/or lupuslike disease, and karyotype should be performed in patients with SLE or IM with mental retardation.

show abstract

“…Overall, it is a general assumption that the cells with sSMC determined in a tissue are somehow representative for the cells with sSMC in all other tissues of the patient studied [Papoulidis et al, 2012]. However, this conjecture could only be more checked in detail in exceptional cases.…”

Section: Discussionmentioning

confidence: 99%

“…However, this conjecture could only be more checked in detail in exceptional cases. There are studies showing complete absence of an sSMC in some tissues [Papoulidis et al, 2012] or a high variance of the presence of sSMC in different tissues [Fickelscher et al, 2007]. Still, in the majority of cases in which more than one tissue was studied, the presence of sSMC could be shown in a comparable amount of them [Liehr, 2014].…”

Section: Discussionmentioning

confidence: 99%

Mitotic Stability of Small Supernumerary Marker Chromosomes: A Study Based on 93 Immortalized Cell Lines

Spittel

Kubek

Kreskowski

et al. 2014

Cytogenet Genome Res

View full text Add to dashboard Cite

Small supernumerary marker chromosomes (sSMC) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. However, no detailed studies have been done for the mitotic stability of sSMC so far, mainly due to the lack of a corresponding in vitro model system. Recently, we established an sSMC-cell bank (Else Kröner-Fresenius-sSMC-cellbank) with >150 cell lines. Therefore, 93 selected sSMC cases were studied here for the presence of the corresponding marker chromosomes before and after Epstein-Barr virus-induced immortalization. The obtained results showed that dicentric inverted duplicated-shaped sSMC are by far more stable in vitro than monocentric centric minute- or ring-shaped sSMC. Simultaneously, a review of the literature revealed that a comparable shape-dependent mitotic stability can be found in vivo in sSMC carriers. Additionally, a possible impact of the age of the sSMC carrier on mitotic stability was found: sSMC cell lines established from patients between 10-20 years of age were predominantly mitotically unstable. The latter finding was independent of the sSMC shape. The present study shows that in vitro models can lead to new and exciting insights into the biology of this genetically and clinically heterogeneous patient group.

show abstract

Tetrasomy 9p Mosaicism Associated with a Normal Phenotype in Two Cases

Cited by 18 publications

References 50 publications

Detectable Clonal Mosaicism in the Human Genome

Detectable Clonal Mosaicism in the Human Genome

Mosaic Tetrasomy 9p: A Mendelian Condition Associated With Pediatric-Onset Overlap Myositis

Mitotic Stability of Small Supernumerary Marker Chromosomes: A Study Based on 93 Immortalized Cell Lines

Contact Info

Product

Resources

About