A further case of familial ring chromosome 20 mosaicism - molecular characterization of the ring and review of the literature

Unterberger, Iris; Dobesberger, Judith; Schober, Harald; Krabichler, Birgit; Lamina, Claudia; Schatz, Ulrich; Zschocke, Johannes; Luef, Gerhard; Kotzot, Dieter; Fauth, Christine

doi:10.1016/j.ejmg.2018.10.016

Cited by 4 publications

(8 citation statements)

References 18 publications

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“…A familial mosaic-tomosaic transmission has been reported for supernumerary r (19), r (20), and r(17) as well (9,39,40). In all the familial cases, the percentage of cells containing the ring was higher in the offspring compared to the mothers and correlated with an earlier epilepsy onset (9,12,19,30,32,39,40). The predominance of maternal transmission has been noted since 1991 by Kosztolanyi, who found that the ring chromosome had a paternal transmission in only two out of 23 families with inherited autosomal ring chromosomes (41).…”

Section: (B) Mosaic R(20)mentioning

confidence: 94%

“…Therefore, subgrouping of r(20) patients may be less strict than previously proposed (10), suggesting that the r (20) structure is more complex than so far envisaged. As a matter of fact, conventional cytogenetic analysis-which undoubtedly represents the gold standard for diagnosis-has been integrated with the characterization of r(20) by molecular analyses only in a few studies thus far (summarized in (20) to the offspring in a mosaic state (Figure 4) (12,19,25,30,32) (Supplementary Table 1). A familial mosaic-tomosaic transmission has been reported for supernumerary r (19), r (20), and r(17) as well (9,39,40).…”

Section: (B) Mosaic R(20)mentioning

confidence: 99%

“…The compensatory UPD mechanism has been found effective in induced pluripotent stem cells (iPSCs) reprogrammed from fibroblasts of ring chromosome patients, as the cellautonomous correction by loss of the unstable ring chromosome and duplication of the normal homolog was observed in the in vitro model (50). However, at least two studies argue against hypotheses 1 and 2, ruling out UPD by microsatellites and SNParray analyses in blood lymphocytes of individuals with r(20) (12,30), as observed in r (14) as well (51).…”

Section: R(20) Mosaic Originmentioning

confidence: 99%

“…Summing up, the evidence so far available argues against hypothesis 2, whereas it does not conflict with hypotheses 3 and 4. However, different studies proposed conflicting interpretations even for the latter pathomechanisms (30). For instance, Surace et al (9) reported on a familial case of r (17) transmitted from mother to daughter, who were both mosaic for a prevalent normal cell line and a minor cell line with r (17) shown by FISH analysis to be complete.…”

Section: R(20) Mosaic Originmentioning

confidence: 99%

“…Further indirect evidence in favor of the ring-opening hypothesis has been recently provided (30). The Authors hypothesize that during meiotic cell division, transmission of a small ring chromosome can pass through safely only if the transmitted chromatid is not involved in sister chromatid exchange at the meiosis prophase.…”

Section: R(20) Mosaic Originmentioning

confidence: 99%

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Ring Chromosome 20 Syndrome: Genetics, Clinical Characteristics, and Overlapping Phenotypes

et al. 2020

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Ring chromosome 20 [r(20)] syndrome is a rare condition characterized by a non-supernumerary ring chromosome 20 replacing a normal chromosome 20. It is commonly seen in a mosaic state and is diagnosed by means of karyotyping. r(20) syndrome is characterized by a recognizable epileptic phenotype with typical EEG pattern, intellectual disability manifesting after seizure onset in otherwise normally developing children, and behavioral changes. Despite the distinctive phenotype, many patients still lack a diagnosis—especially in the genomic era—and the pathomechanisms of ring formation are poorly understood. In this review we address the genetic and clinical aspects of r(20) syndrome, and discuss differential diagnoses and overlapping phenotypes, providing the reader with useful tools for clinical and laboratory practice. We also discuss the current issues in understanding the mechanisms through which ring 20 chromosome causes the typical manifestations, and present unpublished data about methylation studies. Ultimately, we explore future perspectives of r(20) research. Our intended audience is clinical and laboratory geneticists, child and adult neurologists, and genetic counselors.

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