Analysis of a family with recurrent fetal copy number variations in 1p31.1 / 中华医学遗传学杂志

Objective@#To analyze a family with recurrent fetal copy number variations (microdeletion and microduplication, respectively) of 1p31.1 using single nucleotide polymorphism-based array (SNP-array) and G banding chromosomal karyotyping.@*Methods@#Amniocentesis and chorionic villus sampling were performed for a woman during the two pregnancies. Whole genome SNP-array was used to detect genomic imbalance of the fetus. The couple was also subjected to G-banding chromosomal analysis and SNP-array analysis.@*Results@#SNP-array showed a 1p31.1 (70 164 686-83 474 843)×1 and a 1p31.1 (70 164 686-83 479 747) × 3 in the fetuses during the two pregnancies, respectively. SNP array results of the couple appeared to be normal. The mother of the fetuses had a 46, XX, inv(1)(p31.1p32.1) karyotype.@*Conclusion@#The paracentric inversion in chromosome 1 in the gravida probably underlies the recurrent 1p31.1 copy number variations in the fetuses. SNP-array combined with G banding chromosomal analysis are suitable for prenatal diagnosis for recurrent microdeletion and microduplication in the same chromosomal region, and can provide detailed information for genetic counseling.

Systemic Epstein-Barr Virus-Positive T-cell Lymphoproliferative Disease of Childhood Presenting as Hemophagocytic Lymphohistiocytosis with Chromosomal Abnormalities / 임상검사와정도관리

Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (EBV+ T-cell LPD) is characterized by a clonal proliferation of T-cells, which may trigger hemophagocytic lymphohistiocytosis (HLH). Chromosomal abnormalities in patients with HLH are usually found in association with underlying malignancies. We report here a case of systemic EBV+ T-cell LPD of childhood initially presenting with HLH. A 19-year-old man was admitted to the hospital with a 2-week history of fever. Laboratory data revealed pancytopenia, hypertriglyceridemia, high ferritin levels, and abnormalities in liver function tests. EBV infection was confirmed by serologic tests and real-time polymerase chain reaction. Examination of the bone marrow showed histiocytic hyperplasia and hemophagocytosis. Further investigation revealed atypical lymphoid cells expressing EBV-encoded RNA, CD3, CD4, and CD8. A chromosomal analysis displayed a complex karyotype. Despite intensive treatment, the patient died 15 days after initial presentation. In conclusion, systemic EBV+ T-cell LPD of childhood presenting with HLH and chromosomal abnormalities may progress rapidly and be fatal. Therefore, a diagnostic workup for chromosomal aberration is essential.

Relations between results of chromosomal analysis and fetal abnormalities determined by ultrasound

Background: Abnormal chromosome may be abnormal in number or structure of chromosomes related to normal chromosomes or sex chromosomes. One sign of abnormal chromosomes that we can observe during pregnancy is the abnormal ultrasound images. Objectives: To discover the relations between the chromosomal abnormalities and some fetal abnormalities determined by ultrasound. Subjects and method: A prospective descriptive study combined with a retrospective study on 250 pregnant women with fetal abnormalities from Aug 2006 to Aug 2008. Results: Among 250 pregnant women with fetal abnormalities determined by ultrasound taken amniocentesis, rate of late amniocentesis (over 20 weeks) was the highest (50.8%), while rate of ideal amniocentesis (16-20 weeks) only accounted for 29.6%. Abnormal chromosomal rate of multiple abnormalities of fetus statistically significant were higher than that of mono abnormal of fetus (46.8% vs. 18.5%/ p<0.0l). Conclusion: Abnormal phenotype determined by ultrasound; rate of chromosomal disorder was 27.2%.

Follow-up Studies and Clinical Significance of Chromosomal Rearrangement in Childhood Acute Lymphocytic Leukemia / 소아과

PURPOSE: Through routine screening for chromosomal defects present in patients with acute lymphocytic leukemia(ALL) by means of reverse transcription-polymerase chain reaction(RT-PCR), we aimed for earlier detection of recurrences, hence evaluating the progress of the disease after treatment, and forecasting the need for further testing. METHODS: We analyzed 30 patients who visited the Pediatrics Department of Severance Hospital, from January 2002 to July 2003, in whom pre- and post-chemotherapy(post remission induction, post consolidateion and during maintenance) bone marrow samples were available. Among them, periodic RT-PCR examinations were performed in five bcr/abl positive cases, five TEL/AML1 positive cases, and seven dupMLL positive cases to follow the changes in genetic markers. RESULTS: In patients with bcr/abl, all five cases reached complete remission in hematologic examination after induction chemotherapy, but bcr/abl RT-PCR was positive in one case after the treatment, with complete remission reached in just four patients. In the group with TEL/AML1, all five cases reached both hematologic and molecular complete remission after induction chemotherapy. In seven cases with dupMLL, hematologic complete remission was reached in all patients, except one patient who was six months old at diagnosis, who exhibited positive findings for abnormal precursor after induction chemotherapy. CONCLUSION: Earlier detection of recurrence was possible through hematologic and chromosomal anaylsis of patients during follow-up. The most essential factor to detect recurrence considered the timing of bone marrow biopsy. So the procedure must be performed at critical intervals in a patient's course of treatment. In patients with ALL, recurrences by drug-resistant cells occur primarily after one year from the initiation of treatment, so we propose that bone marrow acquisitions to detect recurrences are recommended at one year after the start of treatment, and just before the discontinuation of treatment.

The Optimal Conditions of Chromosomal Analysis in Peripheral Blood / 대한산부인과학회잡지

OBJECTIVE: To find out the optimal conditions of human chromosomal analysis protocol in peripheral blood sample. METHODS: The experiments were made with the variations of phytohaemagglutinin, colcemid, ethidium bromide concentration and the variations of hypotonic solution exposure time. RESULTS: In the experiment on the optimal phytohaemagglutinin concentration, the highest mitotic index in the overall collected cells was obtained in phytohaemagglutinin concentration 15microL/ml. In the experiment on the concentration of mitotic arrestant colcemid, the proper chromosomal state that is meta phase stage and doesn't have many chromosomal crossings or tangles was obtained in colcemid concentration 0.05microg/ml. In the experiment on the optimal exposure time of hypotonic solution(0.075M KCl) treatment, the most suitable intervals between chromosomes were subtained in 20 minutes. In the experiment on the optimal concentration of ethidium bromide to obtain minute chromosomal bands, the best result was when ethidium bromide concentration 5microg/ml or 7.5microg/ml was addition to colcemid concentration 0.02microg/ml. CONCLUSION: The combination of phytohaemagglutinin 15microL/ml, colcemid 0.05microg/ml, hypotonic solution exposure time for 20 minutes is important to the collection of appropriate chromosome state in human chromosomal analysis using peripheral blood. In the case that needs to obtain minute bands, the elongated chromosomes are obtained when ethidium bromide 5microg/ml or 7.5microg/ml in addition to colcemid concentration 0.02microg/ml with the same conditions of phytohaemagglutinin and hypotonic solution.

Jarcho-Levin syndrome: a report of an autopsy case with cytogenetic analysis

Jarcho-Levin syndrome (JLS) is a condition manifested by malformations of vertebral bodes and related ribs. There are two major subtypes spondylocostal dysostosis and spondylothoracic dysostosis, with different survival rates, associated malformations, and inheritance patterns. We have experienced an autopsy case of a premature female fetus with multiple congenital anomalies. She was 30 weeks of gestational age, born as the second baby of twins and expired shortly after birth. A post-mortem examination revealed multiple abnormalities including cervicothoracic hemivertebrae, a diminished number of right-sided ribs, and pulmonary hypoplasia with left diaphragmatic hernia. In addition, there were anomalous rotation of the foregut, unfused pancreas and anomalous drainage of the superior vena cava. Chromosomal analysis showed 46, XX, del(4)(q ter).

Cytogenetic analysis of meningiomas

Cytogenetic analysis of 4 cases of meningiomas from 3 male and 1 female patients is reported. One of male patients suffered from neurofibromatosis type 2. Histologically, the meningiomas were meningotheliomatous (1), transitional (2), and psammomatous (1). Chromosomal abnormalities were found in all cases with a karyotype 45,XY,-22, 45,XY,-16, 45,XX,-2, and 45,XY,t (15p;22q), respectively. Monosomy of chromosome 22 was detected only in the patient with neurofibromatosis type 2. These cytogenetic analysis demonstrates that variable clonal karyotype aberrations exist in meningiomas.

Chromosome Study of the Congenital Anomaly and Mental Retardation in Korean Children

The authors studie 111 cases of congenital anomalies and/or mental retardation. 56cases of congenital anomalies and/or mental retardations were cared and admitted at pediatric department in Han Yang University hospital. 55 cases were in institution for the mentally retarded. The authors studied chromosome analysis about 111 cases with congenital anomalies and/or mental retardation. The results obtained were as follows: A) Mentally retarded children in institution 1. Age distribution was among 5-20 years of age. 2. I.Q. distribution was revealed highest below 35 (in 25 cases) 3. Incidence of chromosomal anomalies was 16.3% in total studied cases. 4. The most common chromosomal anomaly was Down syndrome(12.7%). Other chromosomal anomalies were Poly X female and Edward syndrome 5. I.Q. distribution of Down syndrome patients was revealed most below 35 (over 86% of total cases). B) Congenital anomaly and/or mental retarded patients in admitted or cared in pediatric department 1. Age distribution was highest among 1 month-1year of age in 23 cases. 12 cases were 1 month after birth. 2. Incidence of chromosomal anomalies was 41% in total studied cases. There was no significanl difference in sex ratio. 3. In distribution of chromosomal anomalies, 18 cases were revealed numerical chromosomal anomalies and 5 cases were revealed structural chromosomal anomalies. 4. The most common numerical chromosomal anomaly was down syndrome(30.3%), other 1 case of them was D/D translocation. 5. Structural chromosomal anomalies were 46, XX,5p-,46,XX,t(15p:21q)/46,XX,46,XX/46,XY,46,XY and long Y,46,XY,del(14p) in karyotypes. 6. Classification of diagnosis in congenital anomalies and/or mental retardation was Down syndrome(19 cases), congenital heart disease(14 cases), cleft lip and cleft palate (8 cases), multiple anomalies, hermaphroditism, cerebral palsy, polydactyly, hypospadia, imperforated anus, giant baby, in this order.