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It has been reported that, compared with simple increased nuchal translucency, fetal cases with septated cystic hygroma (CH) are more likely to face perinatal handicaps. However, pediatric outcomes and proper prenatal counseling for this anomaly have not yet been truly defined. We performed this study to determine pregnancy and pediatric outcomes of fetuses with septated CH. We searched records for cases with septated CH and collected data for structural abnormalities, karyotype analysis, and pregnancy outcomes. Fetuses born with septated CH were also evaluated for their pediatric outcomes. Sixty-nine fetuses with septated CH were enrolled in the study. Results showed that chromosomal abnormalities were present in 28 fetuses (40.6%), and the most common aneuploidy was Turner syndrome (n=14, 20.3%); 16 (23.2%) of the remaining cases, in which aneuploidy was not found, had coexistent structural malformations; 25 (36.2%) cases had normal karyotype and morphology. The total number of live births and infants with unfavorable neurologic follow-up were 13 (18.8%) and 2 (2.9%), respectively. Septated CH is associated with poor perinatal outcomes; therefore, karyotype analysis and ultrasonographic anomaly screening should be performed as initial steps, and expectant management should be offered to couples with euploid fetuses that have normal morphology.

Complex chromosomal rearrangements are very rare chromosomal abnormalities. Individuals with a complex chromosomal rearrangement can be phenotypically normal or display a clinical abnormality. It is believed that these abnormalities are due to either microdeletions or microduplications at the translocation breakpoints or as a result of disruption of the genes located in the breakpoints. In this study we describe a 2-year-old child with mental retardation and developmental delay in whom a de novo apparently balanced exceptional complex chromosomal rearrangement was found through conventional cytogenetic analysis. Using both cytogenetic and FISH analysis, the patient's karyotype was found to be: 46,XY,der(5)t(5;7)(p15.1;7q34),t(5;8)(q13.1;8q24.1)dn. A large, clinically significant deletion which encompassed 887.69kb was detected at the 5q12.1-5q12.3 (chr5:62.886.523-63.774.210) genomic region using array-CGH. This deleted region includes the HTR1A and RNF180 genes. This is the first report of an individual with an apparently balanced complex chromosomal rearrangement in conjunction with a microdeletion at 5q12.1-5q12.3 in which there are both mental-motor retardation and dysmorphia., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In this report we describe the first patient ever found to have azoospermia in association with both exceptional complex chromosomal rearrangements and microdeletions at two translocation breakpoints. A 36-year-old male who had been suffering from male factor infertility was admitted to our clinic. The patient also displayed mild dysmorphia. An analysis of the patient's semen revealed azoospermia. GTG banding revealed the presence of an exceptional complex chromosomal rearrangement involving chromosomes 1, 4, 10 and 14. Using subtelomeric FISH analysis, the patient's karyotype was designated as 46,XY,t(1;10)(q43q44;q21q26.1)(CEB108/T7+,D1S3738-;10PTEL006+,D10S2290+, D1S3738+), ins(14;4) (q31.3;q23q33)(D14S1420+; D4S3359+, D4S2930+). Array-CGH analysis revealed two microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions. We suggest that microdeletions at the 4q22.3q23 and 14q31.1q31.3 chromosomal regions associated with both an exceptional complex chromosomal rearrangement and the Homo sapiens chromosome 4 open reading frame 37 (C4orf37) gene located at the 4q22.3q23 region might be associated with male factor infertility., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.

We report, a newborn presenting multiple congenital abnormalities with karyotype; 47,XY,der(7)t(6;7)(pter-p23::p15-->qter),+der(9)t(7;9)(pter-->p15::q21.2--> pter)t(6;7;9)(p23;p15;q21.2)mat[20]. The mother and her phenotypically normal daughter were carriers of a complex chromosomal rearrangement with karyotypes; 46,XX,t(6;7;9)(p23;p15;q21.2)[20]. Paternal chromosomes were normal. In our case the extra derivative chromosome was the result of a 4:2 segregation of the chromosomes involved in translocation during oogenesis. Double partial trisomy in newborns resulting from 4:2 segregation is a rare event, and double partial trisomies of the 6p23-pter and trisomy 9pter-q22 regions have not reported to date.

We report here a prenatal case with de novo supernumerary marker chromosome originating from chromosome 17 in non-mosaic form resulting in normal pregnancy outcome. In this case, a 26-year-old pregnant woman was referred for amniocenthesis and microdeletion Fluorescence In Situ Hybridization (FISH) testing at 18 weeks of gestation due to history of a previous child with Angelman Syndrome. PWS/AS region deletion was excluded by FISH. A de novo supernumerary, non-satellited, monocentric marker chromosome was detected during conventional cytogenetic analysis. With the use of FISH testing, it was found that the marker chromosome originated from chromosome 17. Additionally, the marker chromosome was found not to contain the Smith-Magenis and Miller Dieker syndrome regions. After detailed review of the literature, genetic counseling was given to the family, and the family decided to continue the pregnancy to term. A female child was born at term without any phenotypical abnormalities and clinical complications. Follow-up at 15 months-of-age revealed no developmental abnormalities. To our knowledge, our patient is the first reported prenatal case with a de novo monocentric, supernumerary marker chromosome derived from chromosome 17 in a non-mosaic form that resulting in normal pregnancy outcome.

Purpose: A larynx squamous cell carcinoma (LSCC) is one of the most common forms of cancer and may exhibit various complex karyotypes., Materials and Methods: We used comparative genomic hybridization (CGH) to analyze DNA gains and losses in 15 squamous cell carcinomas that consisted of 4 glottic, 10 supraglottic, and 1 transglottic localization samples., Results: The majority of the chromosomal alterations detected were gains: 3 samples of LSCCs revealed high level amplification, while 6 samples displayed gains in various chromosomal regions (17p, 3p, 4p, 5p, 6q, 8p, 9p, 14q, 18p and Xq). One sample was found to have losses (chromosomes 15q and 22q) and 5 had normal CGH profiles., Conclusion: Many of these gained regions (4p, 5p, 8p, 10q, 18q and Xq) were novel sites, which may harbor oncogene(s) that potentially play an important role in squamous cell tumorigenesis and progression at supraglottic localizations.

Subtelomeric chromosomal rearrangements detected in patients with idiopathic mental retardation and dysmorphic features: Cryptic aberrations involving the subtelomeric regions of chromosomes are thought to be responsible for idiopathic mental retardation (MR) and multiple congenital anomalies, although the exact incidence of these aberrations is still unclear. With the advent of chromosome-specific telomeric Fluorescence In Situ Hybridization (FISH) probes, it is now possible to identify submicroscopic rearrangements of distal ends of the chromosomes that can not be detected by conventional cytogenetic methods. In this study, cryptic subtelomeric chromosomal aberrations were detected in two of ten patients with idiopathic MR and dysmorphic features by using FISH probes of subtelomeric regions of all chromosome arms. A cryptic unbalanced de novo translocation was detected between the subtelomeric regions of the chromosome 10p and 18p in a patient with severe mental retardation, sensorineuronal deafness and several dysmorphic features. In the other patient, with mild mental retardation and dysmorphic features, a de novo subtelomeric deletion of chromosome 2q was found. In conclusion, in both familial and sporadic cases with idiopathic MR and dysmorphic features, the detection of chromosomal aberrations including subtelomeric rearrangements is of great importance in offering genetic counseling and prenatal diagnosis.

Objective: Mutations in KRIT1 cause familial cerebral cavernous malformation, an autosomal dominant disorder affecting primarily the central nervous system vasculature. Although recent studies have suggested that Krev-1 interaction trapped 1 (KRIT1) is a microtubule-associated protein that interacts with integrin cytoplasmic domain-associated protein-1alpha, the function of KRIT1 remains elusive., Methods: We used Western blotting and immunohistochemistry with specific KRIT1 polyclonal antibodies to investigate KRIT1 protein expression in diverse cerebral and extracerebral tissues., Results: Immunostaining demonstrates that although KRIT1 is expressed in a broad variety of human organs, it localizes to the vascular endothelium of each, specifically to capillaries and arterioles. KRIT1 antibody fails to stain fenestrated capillaries in the kidney, the liver, or the red pulp of the spleen, where endothelial cells do not to adhere to one another. In contrast, intense staining is observed in the thymus and the white pulp of the spleen, where specialized blood-organ barriers are formed. Other cell types, including various epithelia, cardiac myocytes, and hepatocytes, also stain with KRIT1., Conclusion: Although KRIT1 expression is seen in every endothelium studied, cerebral cavernous malformation lesions are seen almost exclusively in the central nervous system, suggesting that additional cell type(s) contribute to the pathophysiology of cerebral cavernous malformations. Here, we demonstrate that KRIT1 is also present in cells and structures integral to the cerebral angiogenesis and formation of the blood-brain barrier, namely, endothelial cells and astrocytic foot processes, as well as pyramidal neurons in the cerebral cortex.