Markova et al. Mol Cytogenet (2021) 14:41 https://doi.org/10.1186/s13039-021-00562-1 CASE REPORT Open Access A new case of 17p13.3p13.1 microduplication resulted from unbalanced translocation: clinical and molecular cytogenetic characterization Zhanna G. Markova* , Marina E. Minzhenkova, Lyudmila A. Bessonova and Nadezda V. Shilova Abstract Copy number gain 17 p13.3p13.1 was detected by chromosomal microarray (CMA) in a girl with developmental/ speech delay and facial dysmorphism. FISH studies made it possible to establish that the identifed genomic imbal- ance is the unbalanced t(9;17) translocation of maternal origin. Clinical features of the patient are also discussed. The advisability of using the combination of CMA and FISH analysis is shown. Copy number gains detected by clinical CMA should be confrmed using FISH analysis in order to determine the physical location of the duplicated seg- ment. Parental follow-up studies is an important step to determine the origin of genomic imbalance. This approach not only allows a most comprehensive characterization of an identifed chromosomal/genomic imbalance but also provision of an adequate medical and genetic counseling for a family taking into account a balanced chromosomal rearrangement. Keywords: 17p13.3p13.1 microduplication, Chromosomal microarray analysis, FISH Background which creates the possibility of a non-allelic homolo- Introduction of molecular cytogenetic methods into gous recombination [1]. Te genomic instability of chro- clinical practice, such as CMA, has become a new stage mosome 17 promotes development of a wide range of in the in the genetic diagnosis of human chromosomal clinical manifestations including cerebral morphologi- abnormalities. Tis technique allows to identify a copy cal brain abnormalities, mental retardation, epilepsy and number variations (CNV), establishing their size, bound- tumors [2–4]. aries and genes involved. Te data obtained have made it Te frst cases of 17p13.3 microduplication were possible to describe genomic disturbances leading to spe- reported in 2009 [3]. Accumulation of similar cases led cifc clinical phenotypes and identify a novel microdele- later to formation of 17p13.3 microduplication syndrome tion and microduplication syndromes. (OMIM #613215). Tis is a rare syndrome wherein the Human chromosome 17 is a small chromosome rich critical region overlaps the deletion region in Miller- in genes linked with a number of well-known microde- Dieker Lissencephaly syndrome (OMIM #247200) involv- letion and microduplication syndromes. Over 23% of the ing PAFAH1B1 and/or YWHAE genes on chromosome chromosome 17 short arm consist of low-copy repeats, 17p13.3. Te identifed cases of 17p13.3 microduplica- tion with various sizes and gene contents have diferent mechanisms of occurrence and diferent clinical pheno- *Correspondence: [email protected] Research Centre for Medical Genetics, Moskvorechye St., 1, Moscow, types. Te common clinical features associated with the Russia 115522 disease are a mild or moderate psychomotor retardation, © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. 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Mol Cytogenet (2021) 14:41 Page 2 of 10 hypotonia, abnormalities of hands and feet, cranio-facial telangiectasia of the frontal region, widely spaced nip- dysmorphism including a high forehead with frontal ples, a short lingual frenum. bossing, hypertelorism, a small nose and a small mouth Te child had in the neonatal period a syndrome of [3, 5, 6]. central nervous system depression, feeding difculties, In this study we report the clinical and molecular cardiopathy (clinically unimportant patent foramen ovale cytogenetic characterization of a new case with duplica- 3 mm), cephalohematomas of the parietal bones, intrau- tion of chromosome 17 region p13.3p13.1. terine infection (conjunctivitis). She had no clinical or electrographic seizures. Magnetic resonance imaging Methods (MRI) of the brain was not performed. Her psychomotor development was retarded: holds Te CytoScan HD array (Afymetrix, USA) was applied his head from 2 months, turns over from 10 months, sat to detect the CNV across the entire genome following the independently at 10 months of age, walked without sup- manufacturer’s protocols. Microarray-based copy num- port at 19 months, and articulates about 10 words at the ber analysis was performed using the Chromosome Anal- time of examination. ysis Suite software version 4.0 (Termo Fisher Scientifc Physical examination: height 88 cm ( 0.73 SD), weight Inc.) and the results were presented on the International + 12 kg (− 0.70 SD), head circumference 47 cm (− 1.12 SD), System for Human Cytogenomic Nomenclature 2016 decrease in the increase in head circumference to height, (ISCN, 2016). Detected CNVs were totally assessed by frontal bossing, hypertelorism, low-set fssures, small comparing them with published literature and the public mouth, triangular chin, fexion contractures of the elbow databases: Database of Genomic Variants (DGV) (http:// and knee joints, moderate contractures of the fngers, dgv. tcag. ca/ dgv/ app/ home), DECIPHER (http:// decip her. planovalgus feet (Fig. 1). sanger. ac. uk/) and OMIM (http:// www. ncbi. nlm. nih. gov/ omim). Genomic positions refer to the Human Genome Results February 2009 assembly (GRCh37/hg19). CMA revealed a 10.5 Mb pathogenic duplication FISH was carried out using chromosomal preparations in terminal region of chromosome 17 afected 285 from cultured peripheral blood lymphocytes following genes, 182 of which are known OMIM-morbid genes the manufacturers’ protocols. DNA probes for subtelo- (Fig. 2a). Te molecular karyotype of the proband meric regions of the short arm of chromosomes 17, the (according to ISCN 2016) was thus: arr[hg19] 17p13 short arm of chromosome 9, centromere region of chro- .3p13.1(525_10512077)×3. mosome 17, pericentromeric heterochromatin of chro- FISH with DNA probe for subtelomeric region17p was mosome 9 (Sub-telomere 17pter, Sub-telomere 9pter, SE performed for the targeted validation of detected CNV. 17 (D17Z1), SE 9 (classical); KREATECH), whole chro- FISH-analysis established that this segment had translo- mosome probes for the short and long arms of chromo- cated from the short arm of chromosome 17 (Fig. 3a). some 17 (XCAP 17 short, XCAP17 long, KREATECH) To fnd out the origin of the identifed rearrangement, were applied. FISH analysis of the proband’s parents was undertaken. Te analysis was carried out using an AxioImager M.1 epifuorescence microscope (Carl Zeiss) and an Isis digi- tal image processing computer program (MetaSystems). Case presentation Te patient, a girl 2 years 3 months old, was referred for CGH due to delayed psychomotor and speech develop- ment. Pedigree burdened, mother’s brother has mental retardation. Te girl is the frst child of healthy non-consanguin- eous parents. Pregnancy proceeded with the threat of termination, premature aging of the placenta and oli- gohydramnios from 25 weeks, isthmic-cervical insuf- fciency (cervical pessary from 30 weeks). Childbirth at 38–39 weeks, weight 3350 g (+ 0.14 SD), height 52 cm (+ 1.45 SD), head circumference 35 cm, chest circum- ference 34 cm, Apgar score was 7/8, multiple stigmas Fig. 1 Clinical presentation of the patient of dysembryogenesis at birth—broad nasal bridge, Markova et al. Mol Cytogenet (2021) 14:41 Page 3 of 10 Fig. 2 CMA results showing about 10.5 Mb duplication of the 17p subterminal region (a) and a normal result of the chromosome 9 (b) Markova et al. Mol Cytogenet (2021) 14:41 Page 4 of 10 Fig. 3 FISH results. a FISH analysis with the chromosome 17 subtelomeric (17pter, green) and chromosome 17 centromeric (red) probes. b FISH analysis with a partial chromosome painting for short (green) and long (red) arms of chromosome 17. c FISH analysis with WCP of chromosome 17, chromosome 9 subtelomeric (9pter, green) and chromosome 9 pericentromeric heterochromatin (blue) probes. d FISH analysis with chromosome 9 subtelomeric (9pter, green) and chromosome 17 centromeric (red) probes Te FISH analysis of the proband’s mother using arm- been translocated distal to the 9p subtelomere region in specifc DNA probes for chromosome 17 revealed derivative chromosome 9 (Fig. 3c). presence of a fuorescent signal corresponding to the Te FISH analysis of the proband’s mother using a 9p material of the short arm of chromosome 17 on one of subtelomeric DNA probe discovered three fuorescent homologues of chromosome 9 (Fig. 3b). signals, two of which were observed on chromosomes Te father had