E.C.A. - EUROPEAN CYTOGENETICISTS ASSOCIATION NEWSLETTER No. 23 January 2009 The internet page on small supernumerary marker chromosomes (sSMC) Thomas Liehr Institute of Human Genetics and Anthropology, Kollegiengasse 10, D-07743 Jena, Germany Introduction al., 2007). According to a recent definition, small Thus, sSMC research is a quickly progressing supernumerary marker chromosomes (sSMC) are field. To provide here an up to date information structurally abnormal chromosomes that cannot source we have set up an internet page on sSMC be characterized unambiguously by conventional in 2006 – the sSMC homepage. We here present banding cytogenetics alone, and are equal in size this page and explain how it is constructed and or smaller than a chromosome 20 of the same can be used. metaphase spread. sSMC can be present addition- ally 1) in a karyotype of 46 normal chromo- How to find the sSMC-homepage somes, (2) in a numerically abnormal karyotype The sSMC-homepage can be entered in via (like Turner- or Down-syndrome) or (3) in a the three following addresses: structurally abnormal but balanced karyotype - http://markerchromosomes.ag.vu/ (e.g. Robertsonian translocation or ring chromo- - http://markerchromosomes.wg.am/ some formation. In contrast, an SMC larger than or chromosome 20 usually can be identified based - http://www.med.uni-jena.de/fish/sSMC/ on chromosome-banding (Liehr et al., 2004). 00START.htm (direct) sSMC are present in 0.075% of prenatal cases but only in 0.044% of postnatal cases. In patients The basic structure of sSMC-homepage with fertility problems 0.125% are sSMC- Entering the sSMC-homepage one will see an carriers. In (develop)mentally retarded patients, interactive start page as shown in Fig. 1; the the sSMC-rate is elevated to 0.288%, similar as figures and brackets added on the left side of the in prenatal cases with ultrasound abnormalities figure are not present online, but help in the (Liehr and Weise, 2007). First described already following to explain the different subsections 1 in 1961 (Ilbery et al., 1961), it is now known that through 8. in 70-74% of the cases a de novo sSMC have no 1. On top of the start page the topic of this phenotypic effect (Graf et al., 2006; Liehr and internet site is given, that is sSMC; in Weise, 2007). Nonetheless, in at least 31-50% of addition (but not shown in Fig. 1) e-mail the cases in which an sSMC is detected in addresses of the author, the day of last update prenatal diagnostics, the pregnancy is terminated and the number of visitors can be found. At (Kumar et al., 1997; Shaffer et al., 2004). i.e. in a present, there are between 200 and 300 certain percentage of potentially healthy children visitors per month. with sSMC, an abortion is induced. This situation 2. In this part of the page the aims of the sSMC- can only be improved by providing more and homepage are listed, i.e. collect all available more reliable information on sSMC. case reports on sSMC from the literature, According to personal experience of the define critical regions for partial trisomies author, being contacted by consultants from all due to the presence of sSMC, provide over the world, the main problem is the lack of information for patients and clinicians, and sound information on ‘their specific case’. A step offer the possibility to characterize sSMC in forward was the suggestion of a first genotype- detail. Also a suggestion for management of phenotype-correlation for sSMC (Liehr et al., an sSMC detection is given according to 2006). This paper from the year 2006 was based Hastings et al. (1999) with minor modify- on ~1600 published sSMC cases. Since then the cations. number of sSMC cases characterized at least for 3. Here basic information on sSMC is provided, their chromosomal origin has increased to ~2700 subdivided in six different topics. Fig. 2 plus ~500 sSMC detected in ‘Turner-syndrome shows where the link ‘Synonyms for sSMC’ karyotypes’ (for the latter see Liehr et al., 2007). leads. The references cited on the sSMC- Moreover, sSMC are nowadays studied by chip- homepage are consecutively numbered and technologies for their breakpoints (e.g. Backx et can be accessed via the corresponding green 10 E.C.A. - EUROPEAN CYTOGENETICISTS ASSOCIATION NEWSLETTER No. 23 January 2009 link ‘references of start page’ or ‘references karyotype. The sub-pages accessible here are of this sub-page’, e.g. the link ‘Frequency of explained below and in Figs. 4 and 5. sSMC’ leads to a submenu as shown in Fig. 5. A click on one of the four buttons of this 3. sections leads to sub-pages reviewing the 4. This section includes the main content of the current knowledge and theories on sSMC sSMC internet site. Clicking on one of the 33 formation. squares leads to sub-pages, which list all 6. Information on euchromatin characterization available sSMC cases in the literature. on sSMC, uniparental disomy and sSMC as Besides the 24 human chromosomes, nine well as ‘how to use this page’ in general can more specific subsections had to be created. be found here. As sSMC contain mainly centromeric 7. This part is addressed to families with an material and their origin is determined by sSMC carrier. Links are provided to a laymen commercially available - sometimes ‘cross- explanation for the sSMC homepage and to hybridizing’ - satellite probes, the following special patient support groups. Also a leaflet subsections were added: sSMC derived from on sSMC in general, for sSMC(1), inv either #1, #5 or #19, and such derived from dup(15) sSMC(16) and Pallister-Killian- #13 or #21 and #14 or #22. sSMC are also syndrome are available – all set up by and/or reported, of which it is only known that they in cooperation with UNIQUE = rare derive from an acrocentric (acro) or a non- chromosome disorder support group: acrocentric (non-acro) chromosome as well http://www.rarechromo.org/. as multiple sSMC derived from different 8. Legal notice as well as ethical approval for chromosomes, and sSMC additionally present our studies on sSMC are given. in a Down- or in a Turner-syndrome Figure 1: Start page of the sSMC homepage – the different sections 1-8 are explained in the text. 11 E.C.A. - EUROPEAN CYTOGENETICISTS ASSOCIATION NEWSLETTER No. 23 January 2009 Structure of the chromosome-specific sub- According to Liehr et al. (2006) plus in pages between published sSMC cases, a genotype- The links provided in section 4 of the start phenotype correlation in connection with the page (Fig. 1) lead to pages like the example of imbalance caused by the sSMC is depicted. Here sSMC derived from chromosome 2 in Fig. 4. On a disclaimer is also included stating the top of the page four interactive squares standing following: this scheme ‘represents the interpreta- for four types of sSMC cases have been placed. tion of the presently available data on sSMC. It In green: cases without clinical findings can be used for interpretation of cytogenetic (including persons with fertility problems), in findings - however, there are always exceptions red: cases with clinical findings, in gray: cases from the findings to be expected. Some are even with unclear clinical correlation, and in yellow: already described on this page. Thus, please use cases with neocentromeres. A click on one of this simplifying scheme carefully! We do not those four fields leads to lists as shown in Fig. 5a take any responsibility for (mis)interpretation of on the example of a normal case with an this scheme’. sSMC(2) – for more details on single cases see Additionally, information on known cases below. with uniparental disomy (UPD) according to Kotzot (2004) is provided. sSMC = small supernumerary marker chromosome SMC = supernumerary marker chromosome (e.g. {3}) AC / ACH = accessory chromosome {58; 73} SAC = small accessory chromosome {74} ESAC = extra structurally abnormal chromosome {14} extra marker chromosome {7} additional marker chromosome {2} supernumerary micro chromosome {9} Figure 2: Synonyms for sSMC as accessory marker chromosome {10} available on sSMC-homepage when clicking the corresponding extra micro chromosome (e.g. {11}) link on the start page. additional chromosome fragments {32} minute (centric) fragment {33} bisatellited marker chromosomes {102} metacentric chromosome fragment {103} SRC = supernumerary ring chromosome (e.g. {16}) SBAC = small bisatellited additional chromosomes {93} NMC = neocentric marker chromosome {150} SMRC = supernumerary minute ring chromosome {161} references of start page The individual sSMC cases first comes the chromosome number followed by For each of the listed sSMC cases the the information if the sSMC-carrier was following information is provided: gender, age at clinically normal (= O), described with clinical diagnosis, studied material, if the sSMC was de signs (= W) or has a neocentric sSMC (= N). novo or inherited, GTG-banding result including Then the chromosomal breakpoint is given. If grade of mosaicism, final FISH result for the only one sSMC of that specific type has been sSMC (if available, here are also the results from described, the code number finishes with 1-1; i.e. array-CGH-studies added in blue – Fig. 5b), it is variant 1, case number 1. A second identical applied methods, result of UPD test, clinical case obtains 1-2, a second case with one identical symptoms and reference where the information breakpoint but other shape obtains 2-1. The cases was from (see Fig. 5). Additionally, each case are ordered according to the sSMC breakpoint in obtains a unique ID number to be easily the short arm of the corresponding chromosome detectable on the sSMC-homepage. This was starting from pter (= end of the short arm). necessary as identical sSMC cases are often Exception: as acrocentric chromosomes have reported in different articles (e.g.