title: Rare congenital chromosomal aberration dic(X;Y)(p22.33;p11.32) in a patient with primary myelofibrosis.
abstract: BACKGROUND
  Constitutional translocations between sex chromosomes are rather rare in humans with breakpoints at Xp11 and Yq11 as the most frequent. Breakpoints on the short arm of the Y chromosome form one subgroup of t(X;Y), giving rise to a derived chromosome with the centromeres of both the X and Y chromosomes, dic(X;Y). Here, we report a rare congenital chromosomal aberration, 46,X,dic(X;Y)(p22.33;p11.32)[20]/45,X[10], in an adult male.
  
  
  METHODS
  Primary myelofibrosis, a malignant haematological disease, was diagnosed in a 63-year-old man following liver transplantation after hepatocellular carcinoma. By the analysis of the bone marrow sample, the karyotype 46,X,dic(X;Y)(p22.33;p11.32) was detected in all the mitoses analysed and verified with multicolour fluorescence in situ hybridization (mFISH). A cytogenetic examination of stimulated peripheral blood cells revealed the constitutional karyotype 46,X,dic(X;Y)(p22.33;p11.32)[20]/45,X[10]. The cell line 45,X was confirmed with FISH in 35 % of interphase nuclei. The SRY locus was present on the dicentric chromosome. A CGH/SNP array (Illumina) revealed a gain of 153,7 Mbp of the X chromosome and a 803-kbp microdeletion (including the SHOX gene), which were also confirmed with FISH. SHOX encodes a transcriptional factor that regulates the growth of the long bones. The deletion of the SHOX gene together with the Madelung deformity of the forearm and the short stature of the proband led to a diagnosis of Léri-Weill dyschondrosteosis (LWD). The gain of almost the whole X chromosome (153,7 Mbp) was considered a variant of Klinefelter syndrome (KS). The levels of gonadotropins and testosterone were consistent with gonadal dysfunction. A malformation of the right external ear was detected.
  
  
  CONCLUSIONS
  We have reported a structural aberration of the sex chromosomes, dic(X;Y)(p22.33;p11.32). The related genomic imbalance is associated with two known hereditary syndromes, LWD and a KS variant, identified in our proband at an advanced age. Because the breakpoints did not involve cancer genes, we inferred that the two malignancies in the proband were not caused by this abnormality. The possible influence of SHOX haploinsufficiency on the growth regulation of auricular chondrocytes is discussed.
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, U Nemocnice 499/2, Prague 2, 128 08 Czech Republic.
authors: Lenka
authors: L
authors: Pavlistova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, U Nemocnice 499/2, Prague 2, 128 08 Czech Republic.
authors: Silvia
authors: S
authors: Izakova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, U Nemocnice 499/2, Prague 2, 128 08 Czech Republic.
authors: Zuzana
authors: Z
authors: Zemanova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, U Nemocnice 499/2, Prague 2, 128 08 Czech Republic.
authors: Lucie
authors: L
authors: Bartuskova
authors: Department of Medical Genetics, Faculty Thomayer's Hospital, Vídeňská 800, 140 00 Prague 4, Czech Republic.
authors: Martina
authors: M
authors: Langova
authors: Department of Clinical Hematology IKEM, Vídeňská 1958/9, 140 21 Prague 4, Czech Republic.
authors: Pavlina
authors: P
authors: Malikova
authors: Center of Oncocytogenetics, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital and First Faculty of Medicine of Charles University, U Nemocnice 499/2, Prague 2, 128 08 Czech Republic ; Department of Cytogenetics, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 08 Prague 2, Czech Republic.
authors: Kyra
authors: K
authors: Michalova
keywords: Klinefelter syndrome variant; Léri-Weill dyschondrosteosis; dic(X;Y)(p22.33;p11.32)