We can Diagnose it if we Consider it. Diagnostic Pitfall for Placenta: Placental Mesenchymal Dysplasia.

Placental mesenchymal dysplasia is an increasingly recognizable abnormality. Early cases have been confused with partial hydatidiform mole. Placental mesenchymal dysplasia is probably under-diagnosed because of being an unfamiliar clinical entity and also mistaken for gestational trophoblastic disease due to the similar sonographic findings of two entities. In this report, we describe the clinical, gross, and histopathological findings of placental mesenchymal dysplasia in two cases. The 33-week-preterm baby of a 26-year-old woman with cardiovascular disease and 342 gram placenta and the 19-week fetus with trisomy 21 of a 40 year-old woman were terminated. Macroscopically thick-walled vessels and microscopically hydropic villous with peripherally localized thick-walled vessels without trophoblastic cell proliferation were observed in both cases. These two cases represent a rare placental anomaly that is benign but it is challenging to distinguish placental mesenchymal dysplasia from an incomplete mole. Placental mesenchymal dysplasia should be included in the differential diagnosis of sonographic findings that show a normal appearing fetus and a placenta with cystic lesions. Placental mesenchymal dysplasia is associated with pregnancy-related hypertension. In conclusion, the most important point is "you can diagnose it if you consider it".

Chromosome abnormalities identified in 457 spontaneous abortions and their histopathological findings.

OBJECTIVE: About 15% of clinically recognized pregnancies result in spontaneous abortion in the first trimester and the vast majority of these are the result of chromosome abnormalities. Studies of chromosomal constitutions of first trimester spontaneous abortions have revealed that at least 50% of the abortions have an abnormal karyotype. In this study we aimed to report the single centre experience of anomalies detected in spontaneous abortions. MATERIAL AND METHOD: We present rare numerical and structural cytogenetic abnormalities detected in spontaneous abortion materials and the histopathological findings of rest material of abortion specimens in our study population. RESULTS: Among 457 cases, 382 were successfully karyotyped while cell culture of 75 cases failed. Cytogenetic abnormalities were detected in 127 of 382 cases (33.24%). Autosomal trisomies were the predominant chromosomal abnormalities with a frequency of 48.8%. Structural chromosomal abnormalities were infrequent in conception materials. The mean age of the mothers was highest in trisomy group, the difference being significantly important (ANOVA p < 0.001). The most frequent chromosomal abnormalities were Turner syndrome, triploidy and trisomy of chromosome 16 followed by trisomy of chromosomes 22 and 21 and tetraploidy. Double trisomies and structural chromosomal abnormalities were rare. Trisomies were more frequent in advanced maternal age. CONCLUSION: Detection of chromosomal abnormalities in spontaneous abortion materials is very important to clarify the causes of loss of pregnancy. Detection of structural chromosomal abnormalities in the cases and their carrier parents can provide proper genetic counseling to these families. These families can be directed towards pre-implantation genetic diagnosis to prevent further pregnancies with complications.

A familial interstitial 4q35 deletion with no discernible clinical effects.

Small deletions on the long arm of distal chromosome 4 do not appear to result in gross congenital malformations, with the most frequently reported clinical findings including mild to moderate intellectual disability, learning disabilities and minor dysmorphic features. Here we report on a cytogenetically detectable familial interstitial chromosome 4 long arm deletion with no discernible phenotypic effects in a mother and her two daughters. The karyotypes of the mother and her two daughters were: 46,XX,del(4)(q35.1q35.2). Based on the results of FISH analyses using whole chromosome specific and subtelomeric probes, the karyotype was designated as: 46,XX,del(4)(q35.1q35.2). ish del(4)(q35-qter)(WCP4+, 36P21+, dJ963K6-). Array-CGH analysis showed an interstitial deletion encompassing 5.75 Mb in the 4q35.1-q35.2 genomic region (chr4:184,717,878-190,469,337; hg19). This is the first report on a cytogenetically detectable familial interstitial chromosome 4 long arm deletion in which there are no discernible phenotypic effects. Both our findings and a review of the literature suggest that more detailed molecular analyses are needed in cases with distal chromosome 4 long arm deletions especially those with breakpoints in the 4q35 region to establish a more precise genotype-phenotype correlation.

Rare structural chromosomal abnormalities in prenatal diagnosis; clinical and cytogenetic findings on 10125 prenatal cases.

UNLABELLED: Objective: The aim of this study was presentation of the ultrasonographic findings and perinatal autopsy of cases with rare chromosomal abnormalities. MATERIAL AND METHOD: A total of 10125 prenatal cases over 17 years including 8731 amniocentesis, 973 chorionic villus sampling, and 421 fetal blood sampling cases were evaluated for prenatal cytogenetic diagnosis. Conventional cytogenetic studies, fluorescence in situ hybridization studies, and Array-CGH analysis techniques were used for genetic analysis. RESULTS: A structural chromosomal abnormality was observed in 95 cases. The most frequently observed structural abnormalities were balanced translocations with a frequency of 53.7% (51 cases) followed by unbalanced translocations (16.8%), inversions (11.6%), supernumerary marker chromosomes (8.4%), duplications (4.2%), deletions and ring chromosomes (2.1%) and complex translocation (1.1%). Rare structural chromosomal abnormalities including de novo balanced translocations, unbalanced translocations, inversions, duplications, deletions, ring chromosomes, and supernumerary marker chromosomes were detected in 24 cases. CONCLUSION: The rate of rare chromosomal abnormalities varies from 2.4% (South East Ireland) to 12.9% (Northern England) in Europe with a total rate of 7.4/10 000 births. In our study, the overall rate of chromosomal abnormality in prenatal cytogenetic diagnosis was 3.7%, similar to South East Ireland. Ultrasonographic and perinatal autopsy findings of the cases with rare structural chromosomal abnormalities are important for proper genetic counseling for further similar cases.

Exceptional complex chromosomal rearrangement and microdeletions at the 4q22.3q23 and 14q31.1q31.3 regions in a patient with azoospermia.

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.

Absence of the SLC22A12 gene mutation in Turkish population with primary gout disease.

The aim of the study was to examine whether SLC22A12 gene mutations might be influenced in primary gout disease. We included 32 patients with diagnosis of primary gout disease and 100 healthy volunteers. DNA was purified from peripheral blood, and all exons of the SLC22A12 gene were sequenced. We did not find any mutations in the SLC22A12 gene in all of the patients, but found 5 polymorphisms in exons 1 (g.T258C, g.C246T), 2 (g.C1246T) and 8 (g.T8011C) and in intron 9 (g.C8577T). However, we have not found any significant differences in the frequency of the individual genotypes between patients with primary gout disease and control group. In addition, the polymorphisms were not associated with hyperuricemia in our patients with primary gout disease. There was no previously reported mutation/polymorphisms of SLC22A12 gene in Turkish population. Our study is the first one in Turkish population and suggests that there is no association between primary gout disease and SLC22A12 gene polymorphisms. Sequence changes in the promotor and intronic regions of SLC22A12 gene should be investigated further with larger case groups.

A 5q12.1-5q12.3 microdeletion in a case with a balanced exceptional complex chromosomal rearrangement.

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.

A patient with Down syndrome with a de novo derivative chromosome 21.

Pure partial trisomy of chromosome 21 is a rare event. The patients with this aberration are very important for setting up precise karyotype-phenotype correlations particularly in Down syndrome phenotype. We present here a patient with Down syndrome with a de novo derivative chromosome 21. Karyotype of the patient was designated as 46,XY,der(21)(p13)dup(21)(q11.2q21.3)dup(21)(q22.2q22.3) with regard to cytogenetic, FISH and array-CGH analyses. Non-continuous monosomic, disomic and trisomic chromosomal segments through the derivative chromosome 21 were detected by array-CGH analysis. STR analyses revealed maternal origin of the de novo derivative chromosome 21. The dual-specificity tyrosine (Y)-phosphorylation regulated kinase 1A (DYRK1A) and Down Syndrome Critical Region 1 (DSCR1) genes that are located in Down syndrome critical region, are supposed to be responsible for most of the clinical findings of Down syndrome. However, our patient is the first patient with Down syndrome whose clinical findings were provided in detail, with a de novo derivative chromosome 21 resulting from multiple chromosome breaks excluding DYRK1A and DSCR1 gene regions.

Aberrations of chromosomes 9 and 22 in acute lymphoblastic leukemia cases detected by ES-fluorescence in situ hybridization.

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.

Pure and complete 12p trisomy due to a maternal centric fission of chromosome 12.

Pure and complete 12p trisomy are rare. Here, we report on a unique patient with trisomy 12p syndrome due to centric fission of maternal chromosome 12. Conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques revealed the proposita's karyotype to be 47,XX,+fis(12)(p10)mat whereas the maternal one was 47,XX,-12,+fis(12)(p10),+fis(12) (q10). This is the first report on centric fission of chromosome 12 leading to stable telocentrics, each with a fully functional centromere. Our observation shows that the centric fission of chromosome 12 can be a new mechanism for generation of a partial centromere and trisomy 12p syndrome.

Prenatal diagnosis of ß-thalassemia and other hemoglobinopathies in southwestern Turkey.

Our aim was to evaluate the prenatal diagnosis of ß-thalassemia (ß-thal) and other hemoglobinopathies in a region with high frequency. After detection by premarital or antenatal screening, 312 patients underwent 420 prenatal diagnostic procedures for 407 fetuses in a 10-year period. Fetal samples were collected by chorionic villi sampling (CVS) in the first trimester and amniocentesis and cordocentesis in the second trimester. Mutation analyses of ß-globin and cytogenetic analyses were performed and the most common mutations detected were: IVS-I-110 (G>A), IVS-II-1 (G>A), IVS-I-6 (T>C) and IVS-II-745 (C>G). Hb S [ß6(A3)Glu→Val, GAG>GTG)] was the most common hemoglobin (Hb) variant with a frequency of 6.3%. Among 407 fetuses, 105 (25.8%) were diagnosed as affected, while 201 (49.4%) were carriers and 101 (24.8%) were normal. Cytogenetic analyses revealed nine fetuses (2.3%) with numerical chromosomal abnormalities as regular or mosaicism. Prenatal diagnosis of common hemoglobinopathies is safe and effective. Performing cytogenetic analysis in excess fetal material is an acceptable option.

Maternal origin and clinical findings in a case with trisomy 22.

We report a newborn girl with multiple congenital anomalies whose chromosomal analysis showed complete trisomy 22. Her phenotype included microcephaly, epicanthus, hypertelorism, micrognathia, cleft palate, microtia, and preauricular tag. She died in the 24th post-natal hour. Trisomy 22 was shown by fluorescence in situ hybridization technique and the parental origin of the extra chromosome was found to be maternal by DNA microsatellite marker analysis of chromosome 22. Postmortem examination revealed the presence of atrioseptal defect and stasis in the biliary canals. We believe that this patient will contribute to the literature both by clinical findings and short life span associated with maternal origin of extra chromosome 22.

An unusual case of chromosome 22q11 deletion syndrome with psychiatric disorder, hypoparathyroidism and precocious puberty.

Deletions of chromosome 22q11 cause a wide range of phenotypes; even affected members from the same family may present with different phenotype. We present an 11-3/12 year-old boy who has 22q11 deletion in a hitherto unreported combination with psychiatric disorder, hypoparathyroidism and precocious puberty. Whether precocious puberty is a clue for chromosome 22q11 deletion syndrome is also discussed.