Chromosome Analysis In Patients Research Articles

Genetic evaluation of newborns with critical congenital heart defects admitted to the intensive care unit

Rapid and efficient diagnostics is crucial for newborns with congenital heart defects (CHD) in intensive care unit (ICU) but is often challenging. Given that genetic factors play a role in 20-30% cases of CHD, it is likely that genetic tests could improve both its speed and efficiency. We aimed to analyze the utility of rapid and cost-effective multiplex ligation dependent probe amplification analysis (MLPA) for chromosomal analysis in newborns with critical CHD. One hundred consecutive newborns admitted with critical CHD to the ICU were included in the study. Those with normal MLPA findings were further tested by chromosomal microarray and clinical exome sequencing. Overall, pathogenic/likely pathogenic variants were determined in ten (10%) newborns by MLPA, three (3%) by chromosomal microarray, and three (3%) by clinical exome sequencing. The most common variant detected was deletion of 22q11.2 region.Conclusion: MLPA is fast and cost-effective analysis that could be used as the first-tier test in newborns with critical CHD admitted to the ICU. What is Known: • MLPA is an established method for chromosome analysis in patients with CHD, but detection rate in newborns with critical CHD is unknown. What is New: • Study suggests that detection rate of casual variants using MLPA in newborns with critical CHD is 10%.

The Role of Chromosome Analysis in Patients with Recurrent Pregnancy Loss

Purpose: Recurrent pregnancy loss (RPL) is called as loss of two or more clinically defined pregnancies. The causes of RPL include chromosomal abnormalities, endocrinological disorders, autoimmune problems, uterine anomalies, and thrombophilic factors. In this study, we aimed to discuss the results of chromosomal analysis of couples who had experienced RPL in central Anatolia and their relationship with RPL. Materials and Methods: A total of 1420 subjects, 721 females and 699 males with two or more RPL, were included in the study. Chromosome analysis was performed using standard cytogenetic GTG banding technique using peripheral blood lymphocytes. All chromosomes were examined for numerical and structural chromosomal abnormalities. Results: Normal chromosome formation,46, XX in 698 people and 46, XY in 680 people, was detected in a total of 1378 people (97%). Normal chromosome variant was detected in 15 patients (1%), most commonly 46,XX,9qh+ (0.28%) in 4 patients and 46,XY,9qh+ (0.21%) in 3 patients. In addition, 12 patients had balance reciprocal translocation (0.8%), 6 patients had robertsonian translocation (0.4%), 45,XX,rob (13;14) (q10;q10) in 4 patients, and 45,XY,rob(13;14)(q10;q10) in 2 patients. Conclusion: In this study, chromosomal translocations were the most important cause of RPL in the chromosomal analysis of the parents (n=18; 1.2%). Approximately 2% of individuals with RPL have numerical and structural chromosomal abnormalities such as reciprocal or robertsonian translocations, inversions, and sex chromosomal abnormalities. In order to have healthy babies, preimplantation genetic diagnostic tests should be recommended to the patients by obstetricians, medical geneticists and clinical embryologists who are involved in reproductive medicine.

Cytogenetic analysis of 10,286 cases with male infertility

Chromosome analysis of 10,286 cases with male infertility and to discuss the genetic causes of male infertility. 10,286 patients with azoospermia and oligoasthenozoospermia were collected in the present center from January 2009 to January 2013.Peripheral blood lymphocyte culture and chromosome analysis were performed. In all the 10,286 cases with azoospermia and oligoasthenozoospermia, 8,401 cases showed normal karyotype, 538 cases had chromosome polymorphism, accounting for 5.2% and 1,378 cases had chromosomal abnormalities with a frequency of 13.4%; Conclusions: Genetic factors are closely related to the occurrence of azoospermia and oligoasthenozoospermia, and chromosome analysis in patients with male infertility is necessary.

21 - Characterization of Chromosome Translocation Breakpoints in Leukemia Using Whole Genome Mate-Pair Sequencing

Translocations are common in hematological neoplasms, some of which are known to play critical roles in disease pathogenesis. However, the clinical significance of the remaining translocations, particularly the uncommon ones, remains unknown due to lack of effective characterization methods. We developed a simple and straightforward strategy, employing mate-pair sequencing, free online data analysis tools and Microsoft Excel, to characterize breakpoints of translocations. Using this strategy, we characterized three translocations detected by chromosome analysis in patients with leukemia. The results demonstrated a fusion between KAT6A intron 16 and CREBBP intron 1 (leading to a type I KAT6A/CREBBP gene fusion) in a recurrent t(8;16)(p11.2;p13.3) translocation, and two different enhancer-MECOM gene fusions in two cytogenetically indistinguishable t(2;3)(p23;q26.2) translocations. These findings revealed possible contributions of the translocations to the disease pathogenesis and also showed that this strategy is efficient and effective, and it can be easily adopted in cytogenetics laboratories.

Tigroid pattern of cerebral white matter involvement in chromosome 6p25 deletion syndrome with concomitant 5p15 duplication.

Sub-telomeric deletions of the short arm of chromosome 6 are a well-described clinical entity characterized by developmental impairment, hypotonia, eye abnormalities and defects in the heart and kidneys. Chromosome 5p terminal duplication is a rarer entity, associated with developmental impairment and facial dysmorphism. We report a 3-year-old patient with a chromosome 6p25.1pter deletion and chromosome 5p15.1pter duplication who had global developmental impairment and unusual cerebral white matter changes, with hypoplastic corpus callosum and cerebellar vermis on magnetic resonance imaging -brain scan. We discuss the differential diagnosis to consider in patients with this appearance on magnetic resonance imaging -brain scan and reiterate the need for chromosome analysis in patients with this pattern of developmental anomaly. Tigroid pattern of cerebral white matter involvement has not been reported in chromosomal deletion/duplication syndromes. With the increasing use of molecular karyotyping for patients with multiple congenital anomalies and developmental delay, it is important to consider the exact size and nature of chromosomal deletion/duplication, in order to provide families with prognostic information and recurrence risk. This in turn, will help provide valuable information regarding the natural history of rare chromosomal imbalances.

Diagnostic yield of chromosome analysis in patients with developmental delay or mental retardation who are otherwise nondysmorphic

There is a standard recommendation that chromosomes be obtained in any patient who presents with developmental delay (DD) or mental retardation (MR) regardless of whether or not they have dysmorphic features. Increasingly, if patients are physically well-formed, the option to perform a karyotype is questioned because of the presumed low yield of a chromosomal abnormality. We hypothesize that patients with DD/MR who are non-dysmorphic do not have abnormal chromosomes at a rate high enough to warrant obtaining a karyotype on all patients in this population. A retrospective analysis of patients with DD/MR who were non-dysmorphic was performed. The total number of subjects was 134. Of these, 120 patients were recommended to have high-resolution chromosomes performed, among whom seven were lost to follow-up. In the remaining 113 patients, all had normal karyotypes. Three subjects were found to have fragile X syndrome, accounting for 3% of the males. One subject had a pathological mutation in MECP2. Our yield of chromosome analysis in non-dysmorphic patients with DD/MR is less than that previously described. The role of array-comparative genomic hybridization (array-CGH) as an auxiliary or alternative procedure in this patient population will be discussed.

P-507: Embryoscopy for direct visualization and direct chorionic villi sampling for missed abortion

To utilize Embryoscopy to obtain accurate information for genetic counseling by visualizing the fetus to evaluate structural abnormalities and to obtain direct chorionic villi biopsies for chromosome analysis in patients with missed abortion after documented fetal heart activity. Retrospective chart review. Embryoscopy was performed on nine patients with missed abortion after documented loss of fetal heart activity. Embryoscopy was performed in conjunction with direct chorionic villi biopsies and suction dilatage and curetage. Using saline as the distending medium, a 3 mm hysteroscope was inserted into the gestational sac to evaluate the fetus for structural abnormalities and to obtain directed chorionic villi biopsies. Fetal growth and development was evaluated then compared to normal fetal growth and developement which correlated with the fetal gestational age. Products of conception, labeled as chorionic villi, were sent for chromosome analysis. Of the nine patients studied, all nine fetuses were structurally abnormal when compared to expected embryonic development at the documented gestational days. Chromosome analysis of the embryoscopic directed biopsies revealed four abnormalities, which included: 69 XXX, 47 XX+9, 47 XX+11, and 70 XXY+22. The remaining five tissue cultures from products of conception yielded karyoptype 46 XX, which were suspected maternal tissue contamination. With the proximity of chorionic villi to the maternal circulation, inevitable mixing of maternal and fetal cells occur. Viable maternal cells rather than abnormal or nonviable fetal cells are more likely to grow in the culture medium. Up to 90% of products of conception sent for chromosome analysis return as 46 XX. (1) When products of conception are sent for chromosome analysis, maternal cells rather than fetal cells are often karyotyped. Chromsome analyses reporting 46 XX for products of conception will have an attached disclaimer that states the analysis could be contaminated by maternal cells. Inaccurate information is reported regarding fetal genetics, leading to faulty genetic counseling for future pregnancies. Embryoscopy allows direct observation of fetal structures and allows direct chorionic villi biopsies to provide more accurate fetal genetic information. Improvement in fetal genetic assessment provides better data for more acurate genetic counseling. Embryoscopy with direct observation of fetal structures and direct chorionic villi biopsies is more accuratein detecting genetic abnormalities in pregnancies which have ended in missed abortion after previous documentation of fetal heart activity. In addition to helping couples progress through their grief, accurate fetal assessment and karyotyping should aid genetic counseling of those couples seeking future conception options. More studies are needed to more precisely define the role of embryoscopy in genetic counseling. (1) American Journal of Obstretrics and Gynecology. 2001July;185(1):198-203.

Prenatal overgrowth and mosaic trisomy 15q25‐qter including the IGF1 receptor gene

Overgrowth is rarely associated with chromosomal imbalances. Here, we report on a male foetus presenting with overgrowth and additional material on the short arm of one of the chromosome 15 in 12% of lymphocytes and 50% of amniotic cells. Parents' karyotypes were normal, indicating a de novo origin for this unbalanced rearrangement. Complementary studies using cytogenetic and FISH studies showed that this additional material resulted in a 15q25-qter trisomy and confirmed the presence of three copies of the insulin-like growth factor 1 receptor (IGF1R) gene, included in the trisomic region. Autopsy performed after termination of pregnancy revealed isolated overgrowth and absence of visceral malformations. The possible mechanisms and origins for the formation of this mosaic pure trisomy are complex. The present observation emphasises the hypothesis that the overgrowth phenotype, frequently reported in patients with trisomy including the 15q26 region, might be causally related to a dosage effect of the IGF1R gene, as well as the importance of chromosome analysis in patients with overgrowth. It also confirms that the overgrowth is of prenatal onset in those observations.

Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: report of two families and review of the literature.

Overgrowth is rarely associated with chromosomal imbalances. Here we report on four children from two unrelated families presenting with overgrowth and a terminal duplication of the long arm of chromosome 15 diagnosed using cytogenetic and FISH studies. In both cases, chromosome analysis of the parents showed a balanced translocation involving 15q26.1-qter. Molecular and cytogenetic studies showed three copies of the insulin-like growth factor 1 receptor (IGF1R) gene. This finding suggests that overgrowth observed in our patients might be causally related to a dosage effect of the IGF1R gene, in contrast to severe growth retardation observed in patients with terminal deletion of 15q. The present observation emphasises the importance of chromosome analysis in patients with overgrowth and mental retardation. Moreover, it further delineates a specific phenotype related to trisomy 15q26.1-qter with macrosomia at birth, overgrowth, macrocephaly and mild developmental delay being the major clinical features.

Apparent Sotos syndrome (cerebral gigantism) in a child with trisomy 20p11.2-p12.1 mosaicism

We report on a child with apparent Sotos syndrome (cerebral gigantism) and partial duplication of the short arm of chromosome 20 mosaicism. Trisomy 20p11.2-p12.1 was diagnosed using cytogenetic and FISH studies. The somatostatin receptor 4 (SSTR4) gene is included in the duplicated segment. This suggests that a dosage effect of this gene might be related to some of the clinical findings observed in our patient. The present observation emphasizes the importance of chromosome analysis in patients with well-delineated but sporadic conditions. Am. J. Med. Genet. 91:273–276, 2000. © 2000 Wiley-Liss, Inc.

Apparent Sotos syndrome (cerebral gigantism) in a child with trisomy 20p11.2-p12.1 mosaicism

We report on a child with apparent Sotos syndrome (cerebral gigantism) and partial duplication of the short arm of chromosome 20 mosaicism. Trisomy 20p11.2-p12.1 was diagnosed using cytogenetic and FISH studies. The somatostatin receptor 4 (SSTR4) gene is included in the duplicated segment. This suggests that a dosage effect of this gene might be related to some of the clinical findings observed in our patient. The present observation emphasizes the importance of chromosome analysis in patients with well-delineated but sporadic conditions.

Chromosome analysis in patients with bladder tumor.

Cytogenetic analysis was performed in 80 patients with bladder tumor. The mitotic activity in patients with tumor G1, G2 and G3 degree of differentiation was not significantly different among them. Most of the patients with noninvasive tumor (G1) had a diploid or nearly diploid chromosome number, but all patients with invasive (G2 and G3) tumor had polyploidy. Marker chromosomes were found in 14 patients and 9 of them developed recurrence very soon. There is a good correlation between the recurrence rate and numerical or structural chromosomal abnormalities. This study emphasizes the importance of the chromosome analysis in the evaluation of therapy and prognosis for patients with bladder tumors.

An analysis of autism in fifty males with the fragile X syndrome.

Fifty males with the fragile X [fra(X)] syndrome, which we consider synonymous with the Martin-Bell syndrome, were identified by a chromosome analysis of patients with developmental delays or mental retardation and family studies of known fra(X) pedigrees. These males were evaluated for autism using three criteria: 1) the DSM III diagnostic criteria for Infantile Autism; 2) the Autism Behavior Checklist (ABC); and 3) the Diagnostic Checklist for Behavior Disturbed Children, Form E2. Sixteen percent of patients fulfilled all of the DSM III criteria for Infantile Autism and an additional 30% fulfilled criteria for Infantile Autism Residual State. Thirty-one percent of patients had autism using the ABC checklist but none of the patients fit the classical Kanner syndrome as described by the E2 questionnaire. Some autistic traits were seen in almost all of the 50 fra(X) patients, including eye avoidance in 90%, handflapping, handbiting or handstereotypies in 88%, and language delays with language peculiarities, usually echolalic speech, in 96%. A pervasive lack of responsiveness was seen in 18% at their present age and in 44% in earlier childhood only. Autistic symptoms are common in the fra(X) syndrome. Therefore, any patient with developmental delays and autism or autistic manifestations should have a chromosomal analysis, including fra(X) examination.

Banded chromosome analysis in patients with treatment-associated acute nonlymphocytic leukemia

We have analyzed G-banded metaphase chromosomes from 20 patients with treatment-associated acute nonlymphocytic leukemia (t-ANLL). Nine patients were previously treated for hematologic malignancies and 11 for solid tumors. The interval from initial therapy to t-ANLL ranged from 35 to 182 mo (median 75.5 mo). Median age at diagnosis of t-ANLL was 58.5 years. Clonal chromosome abnormalities were found in 19 patients (95%). Loss or partial deletion of the long arm of chromosomes #5 and/or #7 were most common, occurring in nine patients. These abnormalities were associated with hypodiploid complex karyotypes. Other nonrandom abnormalities recurring among karyotypes with abnormalities of chromosome #5 included loss of one #18, partial deletion of the long arm of chromosome #2, ring chromosomes, and a Philadelphia (Ph 1) chromosome. We also identified a group of five patients whose only karyotypic abnormality was addition of whole chromosomes. The remaining five patients had other karyotypic abnormalities, the most common of which were structural rearrangements in a pseudodiploid clone. Combined data from our study and the three previously published large series of patients with t-ANLL studied with banding suggest a relationship between karyotype and intensity of prior therapy, with abnormalities of chromosomes #5 and #7 occurring more often in the intensively treated patients.

Chromosome analysis in patients with sarcoidosis.

Chromosome analysis of lymphocytes from the peripheral blood of 20 patients with sarcoidosis and 10 healthy controls showed a significantly greater number of hypomodal cells among the patients. Two patients receiving systemic treatment with glucocorticoids had many chromosomal aberrations.

Metronidazole: chromosome analysis in patients treated for Trichomoniasis vaginalis, and the micro-nucleus test in mice

Metronidazole: chromosome analysis in patients treated for Trichomoniasis vaginalis, and the micro-nucleus test in mice

Haptoglobin types in Alzheimer's disease and senile dementia.

There is much neuropathological evidence that Alzheimer's Disease and senile dementia are essentially identical disorders (Stam, 1962; McMenemey, 1963; Jamada and Mehraein, 1968; Lauter, 1970; Torvik, 1970). Family and genetic studies also give support to this opinion, for there appears to be a tendency for both senile dementia and Alzheimer's Disease towards familial aggregation (Zerbin-Rüdin, 1967; Pratt, 1970). An extensive Swedish study has given evidence that senile dementia is determined by a single autosomal dominent gene (Sjögrenet al., 1952). The difference in concordance rates between identical and non-identical twins with senile dementia is in agreement with this hypothesis (Kallmann, 1956). Furthermore, a number of families in which Alzheimer's Disease is transmitted as a regularly dominant trait have been described (Pratt, 1970). For the sporadic cases of Alzheimer's disease a cumulative polygenic action has been assumed (Larssonet al., 1963). Chromosome analysis of patients with Alzheimer's Disease and senile dementia has revealed certain abnormalities (Nielsen, 1968; Bergener and Jungklaass, 1970). Wheelan (1959) found that the MNSs blood groups appear to segregate with Alzheimer's Disease: however, another investigation failed to confirm a significant linkage between blood group genes and Alzheimer's Disease (Feldman, 1969).

Potter's Syndrome

is often associated with the live-born but unresuscitable infant, yet the clinical diagnosis of Potter's syndrome is rarely made by the physician who is resuscitating the infant. This fact warrants brief review of the syndrome and the presentation of three patients on whom chromosome analyses were performed. Potter's syndrome includes the following features: low set and malformed ears; long epicanthal folds; flattened bridge of the nose; small mandible; other facial features described by Potter as well as renal agenesis, pulmonary hypoplasia, oligohydramnios, and amnion nodosum.1-3There are frequent associated skeletal malformations such as clubbing of the hands and feet and other fixed and contracted joints. Similar facial, pulmonary, musculoskeletal, and amniotic findings have been described with a spectrum of renal abnormalities.4,5 The multiple abnormalities of Potter's syndrome and of related syndromes suggest a chromosome defect. To our knowledge, no chromosome analysis of patients with Potter's syndrome