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Раздел 2 Педиатрия
all 20 CLL and one B-ALL case showed BIRC3 deletion, and three CLL and one B-ALL case BIRC3 duplication. All cases with ATM deletion went together with deletion in BIRC3. Only two CLL cases showed deletion in BIRC3, ATM, and TP53simultaneously. Obviously both, deletion and duplication of BIRC3 can be observed rarely in B-ALL. Also BIRC3 duplication can be found in CLL and the prognostic meaning has to be determined in future. The likelihood that TP53 deletions go together with BIRC3 and/or ATM aberrations is quite low. However, as ATM-deletion can, but must not go together with BIRC3-deletions, both regions should be tested both in future CLL-diagnostics to draw correct treatment decisions, namely the treatment with or without fludarabine. Supported in parts by KAAD (fellowship to EA), DAAD (fellowship to MAKO; PROBRAL 57054562 to TL; uni-versitypartnership program of FSU Jena to TL).
CLINICAL AND MOLECULAR CHARACTERIZATION OF A PATIENT WITH A 2Q22.3 TO 2Q24.1 DELETION
Babameto-Laku A.1, Mokini V.1, Roko D.1, Angioni A.2, Mingarelli R.2, Liehr T.3, Dallapiccola B.2
'Service of Medical Genetics, University Hospital "Mother Teresa", Faculty of Medicine, Tirana, Albania 2Direzione Scientifica IRCCS-Ospedale Pediatrico Bambino Gesu, Roma, Italy
Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Jena, Germany
Most of the previously reported cases with interstitial deletion in the long arm of a chromosome 2 have been detected by banding cytogenetic techniques, showing poor breakpoint characterization. Applying array-based comparative genomic hybridization (array-CGH), the detection rate of submicroscopic chromosomal abnormalities improved considerably. Here we report an Albanian boy, five years old, with mental retardation, hypotonia, dysmorphic features and hand/foot abnormalities. A complex cryptic rearrangement of chromosome 2 including a small deletion 547 kb in size (arr[GRCh37/hgl9] 2p12(75,145,737-75,692,546)xl), that overlaps with a copy-number variant region and a deletion of 9.4 Mb (arr[GRCh37/hg19] 2q2 2.3q24.1(145,809,240-155,187,403)x1) were identified by array-CGH. Region 2q22.3 to 2q24.1 encompassed the genes MBD5 and EPC2. Interestingly, haploinsufficiency of MBD5 is known to be associated with microcephaly, intellectual disabilities, severe speech impairment, and seizures, as also seen in the present patient. Furthermore, the present case shares some clinical features with previously reported carriers of deletions within the chromosomal region 2q22 to 2q24.
The present case provides further evidence for a contiguous gene syndrome located in 2q23q24. It adds new information on the potentially critical region, involved genes and clinical features. Even though the ~500bp deletion in 2p12 just seems to be a copy number variant, according to the 'two-hit-model', an influence of such "copy number variants" cannot be completely neglected and suggest other studies.
INFLUENCE OF AFLATOXIN B1 ON COPY NUMBER VARIANTS IN HUMAN LEUKOCYTES IN VITRO
Harutyunyan T.1, Hovhannisyan G.1, Babayan N.1,2, Othman Moneeb A.K..3, Liehr T.3, Aroutiounian R.1
'Department of Genetics and Cytology, Yerevan State University, Yerevan, Armenia 2Institute of Molecular Biology, National Academy of Sciences, Yerevan, Armenia
3Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena, Germany
Aflatoxin B1 (AFB1) is a mycotoxin produced by Aspergillus spec. The latter are worldwide contaminants of food with mutagenic and carcinogenic activities in animals and humans. AFB1 was shown to have deleterious effects on metabolism of eukaryotes in many model systems, including the ability to inhibit DNA replication. An agent that disturbs DNA replication may also have the potential to induce de novo DNA copy number variations (CNVs). Blood samples of three clinically healthy carriers were treated in vitro with AFB1 and chromosome preparations were subjected to parental origin determination fluorescence in situ hybridization (pod-FISH). Probes able to visualize CNVs in 8p21.2 and 15q11.2 were applied. In this setting here for the first time an influence of AFB1 on molecular-cytoge-netically detectable CNVs could be shown. The obtained results indicate that: (i) pod-FISH is a single cell directed, sensitive and suitable method for the analysis of mutagen induced CNVs, (ii) AFB1 has the potential to induce in vitro instability of known CNVs in human leukocytes. This research was supported by MES BMBF (grant number 12GE-004) and partially by State Committee of Science of RA (grant number 14A-1f16).
PARENTAL ORIGIN OF MULTIPLE SMALL SUPERNUMERARY MARKER CHROMOSOMES: EVIDENCE FROM A RARE PRENATAL AND POSTNATAL CASE
Hochstenbach R.1, Nowakowska B.2, Volleth M.3, Ummels A.1, Kutkowska-Kazmierczak A.2, Obersztyn E.2, Ziemkiewicz K.2, Schanze D.3, Zenker M.3, Muschk P.3, Schanze I.3, GerloffC.4, Poot M.1, Liehr T.5 1Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands 2Department of Medical Genetics, Institute of the Mother and Child, ul. Kasprzaka, Warsaw, Poland 3Department of Human Genetics, Otto-von-Guericke University, Magdeburg, Germany
4Universitätsfrauenklinik, Otto-von-Guericke Universität, Magdeburg, Germany
5Universitätsklinikum Jena, Institut für Humangenetik, Jena, Germany
We present two novel cases with different combinations of de novo multiple supernumerary marker chromosomes (sSMCs), each derived from a different chromosome. We determined the gene content, contribution to the clinical phenotype and parental origin of the sSMCs using karyo-typing, fluorescence in situ hybridization, and oligonucle-
РОССИЙСКИЙ ВЕСТНИКПЕРИНАТОЛОГИИ И ПЕДИАТРИИ, 4, 2015
