De Novo Pericentric Inversion of Chromosome 9 in Congenital Anomaly

PURPOSE: The pericentric inversion of chromosome 9 is one of the most common structural balanced chromosomal variations and has been found in both normal populations and patients with various abnormal phenotypes and diseases. The aim of this study was to re-evaluate the clinical impact of inv(9)(p11q13). MATERIALS AND METHODS: We studied the karyotypes of 431 neonates with congenital anomalies at the Pediatric Clinic in Ajou University Hospital between 2004 and 2008 and retrospectively reviewed their clinical data. RESULTS: Chromosomal aberrations were detected in 60 patients (13.9%). The most common type of structural abnormality was inv(9)(p11q13), found in eight patients. Clinical investigation revealed that all eight cases with inv(9)(p11q13) had various congenital anomalies including: polydactyly, club foot, microtia, deafness, asymmetric face, giant Meckel's diverticulum, duodenal diaphragm, small bowel malrotation, pulmonary stenosis, cardiomyopathy, arrhythmia, and intrauterine growth restriction. The cytogenetic analysis of parents showed that all of the cases were de novo heterozygous inv(9)(p11q13). CONCLUSION: Since our results indicate that the incidence of inv(9)(p11q13) in patients with congenital anomalies was not significantly different from the normal population, inv(9)(p11q13) does not appear to be pathogenic with regard to the congenital anomalies. Some other, to date unknown, causes of the anomalies remain to be identified.

Constitutional Pericentric Inversion 9 in Korean Patients with Chronic Myelogenous Leukemia / 대한진단검사의학회지

BACKGROUND: Although the pericentric inversion of chromosome 9, inv(9)(p11q13), is generally considered a normal variation, it is also associated with solid tumors and several hematologic malignancies such as biphenotypic acute leukemia, ALL, AML, and myeloproliferative neoplasms. However, to the best of our knowledge, there have been no reports that suggest an association between CML and constitutional pericentric inversion of chromosome 9. The purpose of this retrospective study was to investigate the frequency and clinical features of CML patients with concomitant inv(9) and t(9;22)(q34;q11.2) variation at our institution. METHODS: We reviewed the bone marrow chromosome database entries between October 2006 and December 2008 to identify patients with concomitant inv(9) and t(9;22) variations. Laboratory and clinical data of the patients were obtained from the electronic medical record system. RESULTS: Among the 51 CML patients, 4 (7.8%) had concomitant inv(9) and t(9;22) variations. CONCLUSIONS: Although the association between inv(9) variation and CML is still controversial, we believe that hematologists should consider the role of constitutional inv(9) variation in CML patients to avoid overlooking the impaired engraftment potential of hematopoietic stem cells harboring inv(9). Therefore, we suggest that more effort should be invested to develop cytogenetic tests for detecting constitutional inv(9) variation in CML patients.

Cytogenetic abnormalities in patients with reproductive dysfunction / 대한산부인과학회지

OBJECTIVE: The aim of this study was to investigate the relationship between chromosome abnormalities and male or female reproductive dysfunction and to be convinced of the role of pericentric inversion of chromosome 9 (inv (9)) on human phenotypes. METHODS: Between Jan. 1995 and Dec. 2003, results of 1713 chromosomal analyses which were referred to our cytogenetic laboratory were analyzed. Study groups consisted of 658 cases of men and 18 cases of women with unexplained infertility, 65 cases of men and 109 cases of women with history of recurrent spontaneous abortion, 78 cases of women with primary amenorrhea, 61 cases of women with secondary amenorrhea and, 382 cases of men and 342 cases of women with no reproductive dysfunction (control group). The incidence of inv (9) among each group was compared with control group. RESULTS: Chromosomal abnormalities were found in 110 cases (16.7%), 2 cases (11.1%), 3 cases (4.6%), 15 cases (13.8%), 29 cases (37.2%) and 10 cases (16.4%) in each group. The incidence of chromosomal abnormalities in male infertility was higher than previous reports, and 10 cases of inv (9) were detected in male infertility group. In cases of women with infertility and secondary amenorrhea, we couldn't find the relevance between reproductive dysfunction and chromosomal abnormality. In cases of women with recurrent spontaneous abortion, 6 cases (5.5%) had autosomal translocation and 7 cases (6.42%) had inv (9). In cases with primary amenorrhea, most chromosomal abnormalities found were related to sex chromosome such as Turner's syndrome, similar to other investigations. Thirty three cases of inv (9) was detected among the whole 1713 chromosomal analyses (1.93%). In cases of male infertility, 10 cases (1.52%) had inv (9), not significantly different with male control group. But 7 cases (6.42%) of inv (9) in women with recurrent spontaneous abortion were significantly higher than female control group (p<0.05). CONCLUSION: Because considerable proportion of patients with reproductive dysfunction had various cytogenetic abnormalities, the chromosomal analysis should be considered as a diagnostic tool in the evaluation of reproductive dysfunction such as infertility, recurrent spontaneous abortion, and amenorrhea. We also found that Inv (9) had a significantly increased incidence in female recurrent spontaneous abortion.

Pericentric inversion of chromosome 9[inv(9)(p12q13)]: Its association with genetic diseases.

Background: The chromosomal polymorphism of short arms of acrocentric chromosomes and heterochromatin variation of Chromosomes 1, 9, 16 and Y have been reported in humans. The pericentric inversion of Chromosome 9 is commonly seen in normal humans and the frequency estimated to be 1 to 3% in general population and inherited in mendalian fashion or might occur spontaneously without any clinical significance. Aim: The aim of the study was to study the frequency of inv(9) and its clinical correlation with human genetic diseases. Materials and Methods:0 The chromosomal analysis using GTG-banding was carried out in 3,392 cases suspected with genetic diseases. Results: The pericentric inversion frequency of different chromosomes in our study was 1.24% and frequency of inv(9)(p12q13) was high (64.29%) compared to other pericentric inversions in our study. A high frequency (9.33%) of inv(9)(p12q13) was detected in children with dysmorphic features and congenital anomalies. Conclusion: As a high frequency of inv(9)(p12q13) detected in children with dysmorphic features, the inv(9) definitely have a role in the abnormal phenotype development. During inversion event there might be loss or suppression of euchromatin chromosome region and hence detailed chromosomal break point study is important to understand the clinical significance of the pericentric inversion of Chromosome 9.

Constitutional Pericentric Inversion of Chromosome 9 inv (9) in Pediatric Leukemia and Stem Cell Transplantation / 대한소아혈액종양학회지

PURPOSE: Pericentric inv (9) occurs in about 0.8~2% of the normal population. The implication of inv (9) in hematological malignancies and/or in stem cell transplantation (SCT) has not been thoroughly elucidated. METHODS: To further delineate the characteristics, we describe our experiences of inv (9) in 2 patients who underwent SCTs and 1 patient with ALL. RESULTS: Case 1. An 11-year-old girl with AML M2 showed 46, XX, inv (9). After remission, her consolidation cycles were associated with slow platelet recovery. She underwent autologous BMT, however, the engraftment was rather slow, and relapsed at 7 months. 2nd remission was achieved after prolonged cytopenia. She underwent reduced intensity unrelated cord blood transplant. Her posttransplant course was uneventful with ANC & gt; 500/microL at D+18 and platelet > 50 k/microL at D+38. Karyotyping showed 46, XY. She is now well at 16 months after 2nd transplant. Case 2. A 10-year-old girl presented with severe aplastic anemia. Karyotyping was normal. She underwent matched sibling transplantation. Her post-transplant course was uneventful with rapid engraftment. Cytogenetics showed 46, XX, inv (9), which was originated from her sister. She is now well at 70 months posttransplant. Case 3. A 3-year-old boy with ALL had a karyotype of 46, XY, inv (9) (p11q12). His clinical course was uneventful. CONCLUSION: The first case showed typical course of delayed recovery after chemotherapy and delayed engraftment after autologous transplantation. inv (9) should be considered in cases of otherwise unexplainable delay in recovery after chemotherapy or delayed engraftment after SCT. Further studies involving larger number of cases should be warranted to delineate the exact role of inv (9) in pediatric leukemia and SCTs.

An Evaluation of Prenatal Triple Marker Screening / 대한진단검사의학회지

BACKGROUND: Maternal serum triple marker screening has become standard in prenatal care to help identify women at risk for neural tube defects (NTDs), trisomy 21 (Down syndrome) and trisomy 18 (Edwards' syndrome). This study was undertaken to evaluate the results of maternal serum triplemarker screening performed in pregnant women visiting Chung-Ang University Hospital and to assess the effectiveness of prenatal triple-marker screening. METHODS: Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) were measured by radioimmunoassay (Amerlex-M 2nd Trimester Kit, Ortho Clinical Diagnostics, Amersham, Aylesbury, UK) in 506 pregnant women visiting Chung-Ang University Hospital. Women at risk for NTDs, trisomy 21 and trisomy 18 were identified using the computer program (HIT Program). Amniocentesis with chromosome analysis was performed in women who had positive screening results. RESULTS: Positive screening results were found in 41 (8.1%) women among 506 pregnant women who had undergone prenatal triple-marker screening between 14 and 22 weeks of gestation. Of these 41 women, 39 (7.7%) had a positive screening results for Down syndrome and 2 (0.4%) for NTDs. Thirty-two women with positive screening results for Down syndrome chose amniocentesis for chromosomal analysis, of which the results showed normal in 28 (87.5%), inv(9) in 3 (9.4%) and 48, XXY, +18 in 1 (3.1%). Although all but one of the fetuses with normal karyotypes and inv(9) were born with normal phenotypes, one pregnancy with 48, XXY, +18 was terminated due to fetal death in-utero. One of 2 pregnancies affected with NTDs was correctly identified, showing meningocele, abdominal wall defect and scoliosis. CONCLUSIONS: Our data confirm chromosome abnormalities or congenital anomalies in about 5% of the pregnancies with positive triple-marker screening results, suggesting an effective prenatal screening test. It has been found that the presence of inv(9) in fetuses might be accompanied by false-positive results for Down syndrome.

A Case of Normal Delivery of a Fetus with Prenatally Diagnosed 47,XYY,inv(9)(p11;q13) / 대한주산의학회잡지

A 35-year-old multigravida woman received triple marker screening tests in 16weeks 2days of gestation. MSAFP and MShCG values were increased, whereas MSuE3 value was decreased. So we performed amniocentesis for karyotyping and confirmed male fetus with 47,XYY,inv(9)(p11:q13). A neonatal survey showed the incidence of XYY male to be approximately 1:1000, the majority of cases are phenotypically normal. XYY males are taller than normal and show delayed mental development. A pericenteric inversion of chromosome 9 that extends from p11 to q13 is considered a normal chromosome variant, but the carrier is at high risk to produce abnormal offspring. As she did not want to terminate her pregnancy, she delivered vaginally in 39weeks 6days of gestation. As a result of physical examination, the neonate showed a normal phenotype. We report it with brief review.