Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Human Cytogenetics Case Report Cytogenet Genome Res 121:302–306 (2008) DOI: 10.1159/000138903 Dynamic mosaicism manifesting as loss, gain and rearrangement of an isodicentric Y chromosome in a male child with growth retardation and abnormal external genitalia I.Y. Iourov a, b S.G. Vorsanova a, b T. Liehr c V.V. Monakhov a I.V. Soloviev a Y.B. Yurov a, b a National Research Center of Mental Health, RAMS, b Institute of Pediatrics and Children Surgery, Roszdrav, Moscow (Russia); c Institute of Human Genetics and Anthropology, Jena (Germany) with some Turner syndrome features is observed in the overwhelming majority of cases (Robinson et al., 1999; Des- Groseilliers et al., 2006), but other additional cell lines in- cluding rearranged chromosomes Y are occasionally ob- served, as well (Hsu, 1994). More precise evaluations of such cases by fluorescence in situ hybridization (FISH) have evi- denced that mosaicism mediated by loss or gain of the rear- ranged Y chromosome could be dynamic, i.e. changing dur- ing ontogeny (Stankiewicz et al., 2001; Codina-Pascual et al., 2004; DesGroseilliers et al., 2006). Consequently, analy- sis of similar cases provides new clues on mitotic mosaicism formation at least in cases of structurally rearranged chro- mosome loss. Moreover, the way of further rearrangement of an already abnormal chromosome is poorly understood. Together, this suggests such case reports to be important both for medical cytogenetic practice and for basic research on formation of chromosome abnormalities. Abstract. Isodicentric chromosomes are considered the most common structural abnormality of the human Y chro- mosome. Because of their instability during cell division, loss of an isodicentric Y seems mainly to lie at the origin of mosaicism in previously reported patients with a 45,X cell line. Here, we report on a similar case, which, however, turned out to be an example of dynamic mosaicism in- volving isodicentric chromosome Y and isochromosome Y after FISH with a set of chromosome Y-specific probes and multicolor banding. Cytogenetic analyses (GTG-, C-, and Q-banding) have shown three different cell lines: 45,X/46, X,idic(Y)(q12)/46,X,+mar. The application of molecular cy- Request reprints from Dr. Ivan Y. Iourov National Research Center of Mental Health, RAMS Moscow 119152 (Russia) telephone: +7 495 9528990; fax: +7 495 9528990 e-mail: ivan_iourov@yahoo.com © 2008 S. Karger AG, Basel 1424–8581/08/1214–0302$24.50/0 Accessible online at: www.karger.com/cgr togenetic techniques established the presence of four cell lines: 45,X (48%), 46,X,idic(Y)(q11.23) (42%), 46,X,i(Y)(p10) (6%) and 47,X,idic(Y)(q11.23),+idic(Y)(q11.23) (4%). Accord- ing to the available literature, this is the first case of dynam- ic mosaicism with up to four different cell lines involving loss, gain, and rearrangement of an idic(Y)(q11.23). The present report indicates that cases of mosaicism involving isodicentric and isochromosome Ys can be more dynamic in terms of somatic intercellular variability that probably has an underappreciated effect on the phenotype. Copyright © 2008 S. Karger AG, Basel Chromosomal mosaicism is a consistent finding in cases of isodicentric Y chromosomes, which represent the most commonly-reported structural abnormality of the Y chro- mosome (Hsu, 1994; DesGroseilliers et al., 2006). This is usually attributed to the instability of rearranged Y chro- mosomes during cell division associated with centromere inactivation (Therman et al., 1986; Haaf and Schmid, 1990; Maraschio et al., 1990). As a result, a 45,X cell line coupled This work was partially supported by Philip Morris USA, Inc. Accepted in revised form for publication by M. Schmid, 8 March 2008.