Genome wide noninvasive prenatal testing detects microduplication of the distal end of chromosome 15 in a fetus: a case report.

BACKGROUND: Noninvasive prenatal testing (NIPT) is the most recent modality widely used in prenatal diagnostics. Commercially available NIPT has high sensitivity and specificity for the common fetal chromosomal aneuploidies. As future advancements in NIPT sequencing technology are becoming promising and more reliable, the ability to detect beyond aneuploidies and to expand detection of submicroscopic genomic alterations, as well as single-gene disorders might become possible. CASE PRESENTATION: Here we present a case of a 34-year-old pregnant woman, G2P1, who had NIPT screening which detected a terminal microduplication of 10.34 Mb on the long arm of chromosome 15 (15q26.1q26.3). Subsequent prenatal diagnostic testing including karyotype, microarray and fluorescence in situ hybridization (FISH) analyses were performed. Microarray testing confirmed and particularized a copy number gain of 10.66 Mb of the distal end of the long arm of chromosome 15. The G-banding cytogenetic studies yielded results consistent with unbalanced translocation between chromosome 15 and 18. To further characterize the abnormality involving the long arm of chromosome 18 and to map the genomic location of the duplicated 15q more precisely, FISH analysis using specific sub-telomeric probes was performed. FISH analysis confirmed that the extra duplicated segment of chromosome 15 is translocated onto the distal end of the long arm of chromosome 18 at band 18q23. Parental karyotype and FISH studies were performed to see if this unbalanced rearrangement was inherited from a healthy balanced translocation carrier versus being a de novo finding. Parental chromosomal analysis provided no evidence of a rearrangement between chromosome 15 and chromosome 18. The final fetal karyotype was reported as 46,XX,der(18)t(15;18)(q26.2;q23)dn. CONCLUSIONS: In this case study, the microduplication of fetal chromosome 15q26.1q26.3 was accurately detected using NIPT. Our results suggest that further refinements in NIPT have the potential to evolve to a powerful and efficient screening method, which might be used to detect a broad range of chromosomal imbalances. Since microduplications and microdeletions are a potential reportable result with NIPT, this must be included in pre-test counseling. Prenatal diagnostic testing of such findings is strongly recommended.

Application of Neural Networks for classification of Patau, Edwards, Down, Turner and Klinefelter Syndrome based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics.

BACKGROUND: The usage of Artificial Neural Networks (ANNs) for genome-enabled classifications and establishing genome-phenotype correlations have been investigated more extensively over the past few years. The reason for this is that ANNs are good approximates of complex functions, so classification can be performed without the need for explicitly defined input-output model. This engineering tool can be applied for optimization of existing methods for disease/syndrome classification. Cytogenetic and molecular analyses are the most frequent tests used in prenatal diagnostic for the early detection of Turner, Klinefelter, Patau, Edwards and Down syndrome. These procedures can be lengthy, repetitive; and often employ invasive techniques so a robust automated method for classifying and reporting prenatal diagnostics would greatly help the clinicians with their routine work. METHODS: The database consisted of data collected from 2500 pregnant woman that came to the Institute of Gynecology, Infertility and Perinatology "Mehmedbasic" for routine antenatal care between January 2000 and December 2016. During first trimester all women were subject to screening test where values of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta human chorionic gonadotropin (ß-hCG) were measured. Also, fetal nuchal translucency thickness and the presence or absence of the nasal bone was observed using ultrasound. RESULTS: The architectures of linear feedforward and feedback neural networks were investigated for various training data distributions and number of neurons in hidden layer. Feedback neural network architecture out performed feedforward neural network architecture in predictive ability for all five aneuploidy prenatal syndrome classes. Feedforward neural network with 15 neurons in hidden layer achieved classification sensitivity of 92.00%. Classification sensitivity of feedback (Elman's) neural network was 99.00%. Average accuracy of feedforward neural network was 89.6% and for feedback was 98.8%. CONCLUSION: The results presented in this paper prove that an expert diagnostic system based on neural networks can be efficiently used for classification of five aneuploidy syndromes, covered with this study, based on first trimester maternal serum screening data, ultrasonographic findings and patient demographics. Developed Expert System proved to be simple, robust, and powerful in properly classifying prenatal aneuploidy syndromes.

Early amniocentesis as a method of choice in diagnosing gynecological diseases.

INTRODUCTION: The aim of prenatal diagnosis is to detect fetal structural and genetic abnormalities. Used are different medical methods, procedures, processes and techniques. For this reason we can speak about the prevention and detection of hereditary diseases and congenital anomalies in the unborn fetus. MATERIAL AND METHODS: The authors analyzed the results of early amniocentesis tests performed during 2009 in Institute for Gynecology, Infertility and Perinatology "Mehmedbasic" in Sarajevo. Performed is 299 analysis of amniotic fluid after amnion puncture done in the Institute or at the Clinic of Gynecology and Obstetrics (GAK) Sarajevo. RESULTS AND DISCUSSION: INDICATIONS FOR THE PERFORMANCE OF EARLY AMNIOCENTESIS WERE: age greater over 35 (84.9%), positive ultrasound markers (1.6%), positive biochemical markers (5.6%) and positive family history for hereditary diseases (7.9%). Detected was 19 pathological cariograms or very high 7% of the total annual number of amniocentesis. An analysis of the distribution of pregnant women in relation to the indication of the result of cytogenetic analysis for each table made positive predictive value (PPV). For indicator age PPV was 0.11, 0.66 for ultrasound markers, for biochemical markers 0.13, for other indications-0.04. The logistic regression model (odds -ratio 11.234 ) indicate a positive ultrasound findings in relation to the year indicates that the risk to gain abnormal fetal karyotype 13 times higher when using only age as an indication for early amniocentesis. Of the 19 pathological cariogram largest number refers to M.Down (10), Sy. Edwards was detected in 2 patients, Sy. Klinefelter in 3, mosaicism in 3 and translocation gene in two of the fetus. CONCLUSION: The authors would like to acknowledge a very high percentage of pathological cariogram risk groups, the extension of indications for RAC indicate the value of ultrasound markers as a good screening methods and the need for social incentives to perform screening tests and early amniocentesis in B&H in order to prevent genetic abnormalities.

Incidence of testicular carcinoma, therapy and quality assesment.

OBJECTIVE: This study aimed to demonstrate incidence, symptoms and therapy management of testicular cancer patients. Also we had evaluated significance of testicular tumor markers. PATIENTS AND METHODS: The study was retrospective, clinical and manipulative, analytical and descriptive and covers the period from 01.01.2000 to 31.12. 2008 with 58 male patients from 16 years upwards. For each patient, the data were analyzed from ambulance and hospital protocol on the Urology Clinic Sarajevo. RESULTS: Incidence of testicular cancer among patients at the Urology Clinic clinical center Sarajevo is on the rise for the last three years (about 20%). Of the 58 patients with testicular cancer, 70% of patients were in age 20-39 years. 47% were patients with right side testicular cancer and 53% were left sided. Walter Reed Hospital tumor classification showed I 50%, IIa 10%, IIb 19% and III 21% of patients. The highest incidence of pathohistological reports showed mixed tumors 46%, seminoma 26%, yolk sack 2%, teratoma 2%, carcinoma embrionale 16%, dysgerminoma 5% and Laydig cell carcinoma 3%. Mixed, seminoma and carcinoma embirionale represents 90% of testicular tumors. betaHCG marker was positive in 53% of patients with seminoma and non seminoma 80%. CEA marker was positive only in 9% of all testicular cancer, LDH showed higher incidence with metastatic seminoma tumor. 27,5% of patients undergone retroperitoneal lymphadenectomy treatment, all patients had radical orchiectomy. CONCLUSION: The common therapeutic procedure in the treatment of testicular tumors are surgical methods radical inguinal orchiectomy, chemotherapy (advanced stages of seminoma and all stages of non seminoma tumor and radiotherapy (early stage seminoma). AFP and betaHCG are excellent markers in the evaluation of surgical and oncology treatment of testicular tumor.

Congenital anomalies of the uterus, and ultrasound diagnostics.

Sonographic detection and evaluation of congenital anomalies of the uterus represent an important segment in the additional therapeutic procedure, that is, treatment of patients with congenital anomalies of the uterus. Besides the primary reason that is manifested in the total cure of the patients, the secondary reason represents the decrease of costs of treatment of congenital anomalies of the uterus. Both descriptive and analytical methods were used in this paper. In 1997 Kurjak and Kupesic compared the sensitivity and specificity of transvaginal ultra sound, color Doppler, hysterosonography and three-dimensional ultrasound during diagnosis of the uterus septum. Representation of pathological findings in our paper in comparison to the examined group is: uterus subseptus = 15.38%, double horned uterus = 10.25%. The examined group includes intrauterine abnormalities of the uterus, analyzing, in that process, individual, pathological entities of intrauterine abnormalities. The research is a prospective, target, clinical study. In the examined group, due to the clinical suspicion of intrauterine abnormalities, 78 patients were examined in the following manner: two-dimensional transabdominal and transvaginal black-and-white and color Doppler ultrasound examinations were made and then three-dimensional transabdominal black-and-white and color Doppler ultrasound examinations. This means that in the detection of congenital anomalies of the uterus, the same sonographic techniques were first applied on the conventional and then also on the multidimensional base. Our research showed that three-dimensional technique is a more reliable diagnostic tool than two-dimensional technique. Sensitivity and specificity rate as well as positive predictive value show that this technique is an extraordinary one for assessing the volume, and position of congenital abnormalities.

Frequency of HPV infection in pre-malignant lesions of cervix at the public institution "Institute for Health Protection of Women and Maternity" of Sarajevo Canton.

INTRODUCTION: About 75% of adolescent and younger adult women get in contact with human papilloma virus (HPV). Some of them develop clinically manifested changes identified on Pap smear as ASCUS (Atypical Squamous Cells of Undetermined Significance) or SIL (Squamous lntraepithelial Lesion). Infection with high-risk genital HPV is considered to be a pre-condition for the occurrence of precancerous lesions and cancer, while in HPV infections with low-risk types such possibilities are extremely rare. MATERIAL AND METHODS: We have analyzed pathological-cytological results of cervical-vaginal smears in the period 1997-2001 and 2001-2005, where HPV typing has been performed. Examinees are divided in two groups--low-risk and high-risk, and are compared with different types of cell abnormalities (ASCUS, SIL, CIN). RESULTS: Low-risk HPV is twice more common than the high-risk oncogenic I-IPV. More than 2/3 of abnormal colposcopy results are verified with presence of HPV infection. CONCLUSION: HPV infection is most common in women 20-30 years of age and is present in all types of epithelial dysplasias.

[Perinatological aspects of mutual relationships between asthma and pregnancy]. / Perinatoloski aspekti uzajamnog odnosa astme i trudnoce.

We have researched influence of asthma on pregnancy, fetus and delivery. We have verified asthmatic pregnant women on the basis of the relevant medical documentation (N=42). Control group is made of healthy pregnant women selected under the FIGO criteria (K=100). We followed up influence of asthma on pregnancy by evaluation of 6 variables which are determinants of pregnancy quality (spontanious abortion, missed abortion, hyperemesis gravidarum, EPH gestoses, prematurity and over-carried pregnancy. Authors didn't find any statistical significance in influence of asthma on pregnancy quality although the level of pathological situations in all researched variables was about 25% higher than in control group. In over-carried pregnancy variable statistically significant low level of cases was found in researched group. Influence of asthma on fetus was monitored with the methods of clinical measurements of fetuses biophysical profile, cardiotocographic index and amnioscopy. Significantly higher participation of pathological situations was found in all three monitored variables within researched group of pregnancies (p<0.01). We have monitored influence of asthma on delivery with the methods of clinical measurement ABS pregnant-asthmatic woman, ABS of the new-born baby, body mass of new-born baby and the kind of delivery. A statistically significant fall of pp O2 (p<0.01) was found as well as declination of actual pH of pregnant-asthmatic woman toward acidosis (p<0.01) during the second delivery stage. Kind of delivery is showing statistically high level of participation of surgical termination of delivery in researched group (SC and vacuum extraction)--(p<0.001).

[The frequency of female genital cancer at Gynecological Department in Cantonal Hospital Zenica--before, during and postwar time in Bosnia-Herzegovina]. / Ucestalost raka zenskih spolnih organa na Ginekoloskom odjeljenju Kantonalne bolnice Zenica--prije, u toku i naklon rata u BiH.

This targeted, retrospective, descriptive, controlled and open study comprises the last decade of the 20th Century and all histologically verified malign tumours at the Cantonal Hospital Zenica. By analysing pathohistological findings, 865 malign genital tumours were found; where the most numerous were cervical maligns (70.06%), then corporal (17.34%), ovarian (10.40%), vulvae 1.16%, vaginal 0.69% and tubal 0.35%. Malign frequency curve shows continual decrease till the war year 1993 and continual increase from that period till 2000. The most frequent type of malign tumour is carcinoma with the frequency of over 98% (70.06% carcinoma planocellulare, 27.86 adenocarcinoma), while recently literature shows a bit over 90% of frequency. More than 3/4 of all malign genital tumours were discovered in nullity and first clinical stages. Results show that approximately 9/10 of all malign processes in female genital tract occurred at uterus. The most frequent are malign tumours that are histologically best differentiated, while the least frequent are those that are insufficiently differentiated. Malign diseases, due to cervical cancer, which encumbers more than half of the cases, mostly afflict age group of 35-49, while the age group 50-64 is mostly afflicted by corporal and ovarian malign tumours. Comparing the year 1991 with 1993, 1995, 1997 and 1999, no statistically significant difference was found occurrence of menarha at women who have cervical, corporal and ovarian malign tumours (p>0.05).

[Therapy of erectile dysfunction--public health aspects]. / Terapija erektilne disfunkcije--javnozdravstveni aspekti.

Erectile dysfunction (ED)--the consistent or recurrent inability of a man to attain and/or maintain, a penile erection sufficient for sexual performance--is a common health condition among men that is largely untreated. It is estimated that some degree of ED affects more than one half of all men over the age of 40--152 million men worldwide. That is a big problem, that needs appropriate treatment. After diagnostic evaluation of the patient, doctor decides what is the best treatment option for the patient, following his health condition. Choice of treatment options: physio-sexual therapy, oral drug therapy, topical drug therapy, transurethral drug therapy, intracavernosal therapy, hormonal treatment, vacuum devices and surgery. Nowadays the most important contemporary treatments of ED are peroral sildenafil and intracavernosal pharmacotherapy using vasoactive medicines. However, these drugs are not suitable to every patient. More noninvasive methods to treat ED, such as oral medication or locally applicable preparations are needed.

[Erectile dysfunction--incidence, causes and risk factors]. / Erektilna disfunkcija--ucestalost, uzroci i rizikofaktori.

The inability of a male to attain and maintain an erection sufficient to allow vaginal penetration is called erectile dysfunction. It is a part of general male sexual dysfunction called impotence, which also includes libidinal, orgasmic and ejaculatory dysfunction. Erectile dysfunction affects millions of men and although it may not mean a total loss of sexual satisfaction, it often creates a mental stress that affects the man's quality of life. Knowledge of erectile dysfunction has increased remarkably over the past decade. Nowadays, about 50-85% of erectile dysfunction patients can be shown to have a somatic cause by modern methods of examination. Erectile dysfunction may also occur as a result of specific illness or medical treatment, and it is often multifactorial in etiology. Erectile dysfunction increases with age.

[Color-Doppler ultrasonography in the diagnostic evaluation of erectile dysfunction]. / Uloga color-Doppler ultrasonografije u dijagnostickoj evaluaciji erektilne disfunkcije.

UNLABELLED: Color-Doppler sonography (CDS) of the cavernosal arteries has received considerable attention since its description in 1985 by Lue et al. Color and Spectral Doppler analysis, provides a useful noninvasive means of evaluating both morphologic and hemodynamic penile abnormalities. CDS is the best method in diagnostic evaluation of patients with erectile dysfunction. It assesses the integrity of the arterial supply to the penis and provides some useful information on the veno-occlusive mechanism. Because the arterial diameter and flow rate change during the different phases of erection CDS is performed after pharmacostimulation with vasoactive agents. Purpose of this study is diagnostic evaluation patients with erectile dysfunction. PATIENTS AND METHOD: We studied 60 patients suspected for vasculogenic ED, and 30 patients suspected for psyhogenic ED, assessing the morphodynamic features of cavernosal arteries by Color-Doppler sonography and their response to contravaernosal injection of prostaglandin E1 (PgE1) and oral dose of Sildenafil citrate. Morphodynamic parameters evaluated by color Doppler sonography included: peak systolic velocity, endodiastolic velocity, inner arterial diameter, index and acceleration of penile blood flow. Patients were divided in the groups: A group (A1--10 patients < 35 years of age, A2--20 patients > 35 years of age) underwent pharmacotest with ICI PgE1; B group (B1--8 patients < 35 years of age, B2--22 patients 35 years age) were tested with oral dose of Sildenafil citrate and C group--30 patients who were also tested with the same drug. CONCLUSION: The CDS may be used to evaluate the hemodynamic parameters of the erectile dysfunction. Arterial insufficiency is suspected with poor blood flow, while veno-occlusive dysfunction is inferred in the face of adequate blood flow and poor erectile response.