113 Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150(1):113–116. © I. Cernakova, M. Kvasnicova, Z. Lovasova, N. Badova, J. Drabek, K. Bouchalova, R. Trojanec, M. Hajduch A DUPLICATION dup(4)(q28q35.2) DE NOVO IN A NEWBORN Iveta Cernakova a , Marta Kvasnicova b , Zuzana Lovasova b , Nora Badova b , Jiri Drabek c , Katerina Bouchalova c , Radek Trojanec c , *Marian Hajduch c a Institute of Biology and Medical Genetics, General Faculty Hospital and The 1 st Faculty of Medicine, Charles University, Albertov 4, 128 00 Prague 2, Czech Republic b Department of Clinical Genetics, Roosewelt Hospital, 975 15 Banska Bystrica, Slovak Republic c Laboratory of Experimental Medicine, Department of Paediatrics, Faculty of Medicine, Palacky University and University Hospital in Olomouc, Puskinova 6, 775 20 Olomouc, Czech Republic e-mail: hajduchm@atlas.cz Received: March 21, 2006; Accepted: April 18, 2006 Key words: Duplication 4q syndrome/Nijmegen breakage syndrome/Cytogenetics/G-band technique/Fluorescence in situ hybridization (FISH)/Polymerase chain reaction (PCR) We report here a case of a newborn with hypotrophy and somatic stigmatization: microcephaly, facial dysmorphism, heart defect and immunodeficiency syndrome. The proband’s karyotype was 46,XY,dup(4)(q28q35.2) de novo with chromosomal breaks in 4% of metaphases. We demonstrate the usefulness of a combination of physical examination, classical cytogenetics, FISH and PCR techniques in order to establish correct diagnosis because of overlap of some clini- cal and cytogenetic features of Nijmegen breakage syndrome (NBS) and duplication 4q in our patient. Although FISH technique detected translocation t(14q;21q) in 4 metaphases, deletion 657del5 in exon 6 of the NBS1 gene associated with NBS in Slavic population was not confirmed. We compare in this report similarity of the clinical picture of our patient, NBS cases and other patients carrying a duplication of the distal part of 4q as described in the literature. INTRODUCTION Duplication of the long arm of chromosome 4 has been already described in more than 60 patients 1, 2 . Most of them result from the meiotic segregation of a paren- tal balanced translocation and associate with a partial monosomy of various segments of other chromosomes. Patients with partial trisomy 4q have variable clinical stigmatization, which is both related to the size of dupli- cated segment of the chromosomal arm 4q and to spe- cific associated monosomy. A review of the literature 2 revealed approximately 20 cases of a pure duplication of 4q spanning the region from q12 to q35. Although simple or pure forms of duplications are less common they serve as a basis for a better understanding of relation- ships between chromosomal anomalies and their clinical manifestations. In this communication we describe clinical, cytoge- netic, FISH and PCR findings in a male newborn with an overlap in some clinical and cytogenetic features of Nijmegen breakage syndrome and duplication 4q. We il- lustrate here the usefulness of the combined views of the clinical geneticist, the cytogeneticist and the molecular geneticist in establishing the correct diagnosis. To our knowledge this is the second case of the pure de novo duplication 4q. MATERIAL AND METHODS Cytogenetic and FISH analysis were performed on cultured PHA-stimulated peripheral blood lymphocytes of the propositus and his parents. Classical cytogenetics was carried out using G-banding. The whole chromosome painting probes 4, 7, 14 and 21 (Vysis) and chromosome specific telomeric probe 4q (Vysis) were used for detec- tion of (the) suspected rearrangements by FISH. PCR diagnosis was performed using a DNA extracted by salting-out method from peripheral blood as described previously 3 . RESULTS Clinical report The boy was born in the 40 th week of physiologic preg- nancy. His birth weight was 2600 g and his length was 52 cm. The child was referred for genetic counselling at the age of 1 month because of somatic stigmatisation. The newborn was hypotrophic and manifested slight hypertonic syndrome. Physical examination at the age of 1 week revealed microcephaly with head circumfer- ence of 31 cm (– 4 SD). The facial features included an- timongoloid slanted palpebral fissures, epicanthic folds, strabismus, broad nasal bridge, prominent beaked nose with anteverted nostrils, low-set malformed ears, high arched palate, micrognathia and a pigmented naevus in