ß 2005 Wiley-Liss, Inc. American Journal of Medical Genetics 140A:46–51 (2006) Overrepresentation of Small Supernumerary Marker Chromosomes (sSMC) From Chromosome 6 Origin in Cases With Multiple sSMC Thomas Liehr, 1 * Heike Starke, 1 Gabriele Senger, 2 Cindy Melotte, 3 Anja Weise, 1 and Joris Robert Vermeesch 3 1 Institut fu ¨r Humangenetik und Anthropologie, Jena, Germany 2 Praxis f. Med. Genetik und Gyna ¨kologie, Regensburg, Germany 3 Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium Received 21 March 2005; Accepted 30 September 2005 Small supernumerary marker chromosomes (sSMC) in human are defined as additional centric derivatives smaller than chromosome 20. In the majority of the cases only one sSMC is present, leading to a more or less stable karyotype of 47,XX,þmar or 47,XY,þmar. In 1.4% of sSMC cases two or up to seven markers of different chromosomal origin are reported. According to the literature a sSMC(6) was present in 33% of the patients with multiple sSMC while sSMC(6) are observed in <1% of cases with a single sSMC. Currently there is no explanation for this striking observation. Here we report on one more unique case with two sSMC, one derived from #5 and the other from #6. Using microdissection/reverse painting, subcentromere-specific multicolor FISH (subcenM- FISH) and multicolor banding (MCB), they could be describ- ed as min or r(6)(::p11.1 ! q11.1::) and r(5)(::p11.112 ! q10::q10 ! p11.112::), respectively. Reversed array CGH using the DNA of the microdissected sSMC as probe con- firmed the FISH results and enabled the rapid mapping of the breakpoints. ß 2005 Wiley-Liss, Inc. Key words: array CGH; chromosome 5; chromosome 6; molecular cytogenetics; small supernumerary marker chro- mosomes (sSMC) INTRODUCTION Small supernumerary marker chromosomes (sSMC) are reported in 0.043% of newborn infants but in 0.410% of persons with mental retardation [Liehr et al., 2004, 2004a]. sSMC are defined as structurally abnormal chromosomes that cannot be identified or characterized unambiguously by con- ventional banding cytogenetics alone, and are generally equal in size or smaller than a chromosome 20 of the same metaphase spread [Liehr et al., 2004a]. The smallest group among the very heterogeneous group of ‘cases with sSMC’ comprises those with multiple sSMC derived from different chromosomes, they provide about 1.4% of sSMC cases [Liehr et al., 2004]. Within this group, there are presently 13 cases with 2, 3 with 4, and 1 each with 3, 5,6, and 7 sSMC per case (for details see Table I) [Callen et al., 1991; Plattner et al., 1993ab; Wiktor et al., 1993; Aalfs et al., 1996; Mackie-Ogilvie et al., 1997; Ulmer et al., 1997, Haddad et al., 1998; Viersbach et al., 1998; Shanske et al., 1999; Vermeesch et al., 1999; Maurer et al., 2001; Nandi et al., 2001; Levy et al., 2002; Beverstock et al., 2003; Reddy et al., 2003; Starke et al., 2003]. All the patients had malformations and/or severe mental retardation. We report on the 14th unique case with two sSMC of different chromosomal origin, provide a review of the literature and point out that the distribution of chromosomal origin in multiple sSMC is markedly different from that of ‘single sSMC.’ MATERIALS AND METHODS Clinical Report The reported girl was born to healthy non- consanguineous parents. Family history is unremark- able with regard to congenital malformations and mental handicap. Pregnancy and term delivery were normal. Birth weight was 3.580 g, length 51 cm, and head circumference 35 cm. No perinatal problems were noted apart from a small fontanelle and bilateral epicanthus. The head circumference developed Grant sponsor: KULEUVEN OT/2002/40 (to J.V.); Grant sponsor: Dr. Robert Pfleger–Stiftung (to T.L.). *Correspondence to: Thomas Liehr, Institut fu ¨r Humangenetik und Anthroplogie, D-07740 Jena, Germany. E-mail: i8lith@mti.uni-jena.de DOI 10.1002/ajmg.a.31048