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Biomedical subjects

S R Patil

Publications and source records attributed to S R Patil.

At least 37 records · Page 2Linked to original sources
PubMed1997

Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461.

PURPOSE: To examine the prognostic significance of extramedullary leukemia (EML) at presentation in patients with t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS: Consecutive patients with t(8;21) treated on Cancer and Leukemia Group B de novo acute myeloid leukemia (AML) treatment studies were examined for the presence of EML (granulocytic sarcoma, subcutaneous nodules, leukemia cutis, or meningeal leukemia) at initial presentation. Clinical features and outcome of t(8;21) patients with and without EML were compared. RESULTS: Of 84 patients with t(8;21), eight (9.5%) had EML manifesting as granulocytic sarcoma (five paraspinal, one breast, and one subcutaneous) or symptomatic meningeal leukemia (n = 1). The pretreatment prognostic variables of t(8;21) patients with and without EML were similar. The hematologic complete remission (CR) rate for t(8;21) patients with EML was 50% versus 92% for those without EML (P=.006). The median CR duration for EML patients was 14.7 months. Patients with EML had a shorter survival (P = 0.002, median 5.4 months versus 59.5 months). This poor outcome may relate to inadequate local (radiation or intrathecal) therapy for patients with spinal or meningeal EML, resulting in residual/recurrent EML following induction chemotherapy (n = 2) or at relapse (n = 1) and permanent neurologic deficits (n = 4). Only one of the EML patients received high-dose cytarabine (HDAC) intensification; this is the only EML patient remaining alive in CR. CONCLUSION: Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.

Adult↗
PubMed1997

Pilot studies for proficiency testing using fluorescence in situ hybridization with chromosome-specific DNA probes: a College of American Pathologists/American College of Medical Genetics Program.

Fluorescence in situ hybridization using chromosome-specific DNA probes is rapidly becoming part of clinical laboratory practice for certain congenital and neoplastic disorders. Current legislation requires proficiency testing for clinical laboratory studies. To evaluate the efficacy of fluorescence in situ hybridization proficiency testing, we invited 19 representative institutions to participate in three pilot studies. One study used probes for the X and Y chromosomes to evaluate metaphase spreads and interphase nuclei. Another study used probes for bcr and abl to detect bcr/abl fusion in interphase nuclei in chronic myelogenous leukemia. The third study used a D22S75 probe to detect microdeletions in metaphase spreads from a patient with velocardiofacial syndrome. The results of these studies demonstrate that proficiency testing with fluorescence in situ hybridization is attainable using either metaphase or interphase preparations, and that either microscope slides or fixed cell pellets are suitable.

Chromosome Mapping↗
PubMed1995

Application of FISH to complex chromosomal rearrangements associated with chronic myelogenous leukemia.

Identification of complex chromosomal rearrangements can be difficult, due either to the limited number and sometimes poor quality of metaphases in bone marrow preparations or to the nature of the rearrangements. Fluorescence in situ hybridization (FISH) using chromosome-specific DNA libraries in conjunction with a cosmid probe for the c-ABL oncogene was performed to substantiate the preliminary G-banded karyotypes of six patients with chronic myelogenous leukemia (CML). Our results indicate that FISH is sufficiently sensitive to detect complex and subtle rearrangements, even in bone marrow preparations with suboptimal metaphases, and can provide valuable corroborative information.

Bone Marrow↗
PubMed1995

Minute supernumerary ring chromosome 22 associated with cat eye syndrome: further delineation of the critical region.

Cat eye syndrome (CES) is typically associated with a supernumerary bisatellited marker chromosome (inv dup 22pter-22q11.2) resulting in four copies of this region. We describe an individual showing the inheritance of a minute supernumerary double ring chromosome 22, which resulted in expression of all cardinal features of CES. The size of the ring was determined by DNA dosage analysis and FISH analysis for five loci mapping to 22q11.2. The probes to the loci D22S9, D22S43, and ATP6E were present in four copies, whereas D22S57 and D22S181 were present in two copies. This finding further delineates the distal boundary of the critical region of CES, with ATP6E being the most distal duplicated locus identified. The phenotypically normal father and grandfather of the patient each had a small supernumerary ring chromosome and demonstrated three copies for the loci D22S9, D22S43, and ATP6E. Although three copies of this region have been reported in other cases with CES features, it is possible that the presence of four copies leads to greater susceptibility.

Abnormalities, Multiple↗
PubMed1994

Linkage analysis of autosomal dominant atrioventricular canal defects: exclusion of chromosome 21.

The association between trisomy 21 and a high incidence of atrioventricular canal defects (AVCDs) indicates that a locus on chromosome 21 is involved in this congenital heart defect. We have investigated whether a genetic locus on chromosome 21 is also involved in familial nonsyndromic AVCDs. Short tandem repeat polymorphisms (STRPs) from chromosome 21 were used for linkage analysis of a family having multiple members affected with AVCDs. In this family, the gene for AVCDs is transmitted as an autosomal dominant with incomplete penetrance. The affected family members are nonsyndromic and have normal karyotypes. Two-point and multipoint linkage analyses produced significantly negative LOD scores for all informative markers. A comparison of the overlapping exclusion distances obtained for each marker at LOD equal -2.0 with the 1000:1 consensus genetic map of the markers, excludes chromosome 21 as the genetic location for AVCDs in this family. The exclusion of chromosome 21 indicates that another gene, not located on chromosome 21, is involved in atrioventricular canal defect formation.

Chromosomes, Human, Pair 21↗
PubMed1993

Incontinentia pigmenti: transmission from father to daughter.

Incontinentia pigmenti (IP) is a well-described genodermatosis that occurs almost exclusively in females. IP is characterized by a distinctive skin eruption and a variable presence of multisystem abnormalities. Pedigree analysis is most consistent with an X-linked dominant trait that is lethal in males. However, 27 reports of IP in males have been published, excluding four patients who had Klinefelter's syndrome. It has usually been assumed that these rare affected males survive because of genetic mosaicism. Mosaic inheritance of IP is also strongly supported by the characteristic distribution of skin findings along Blaschko's lines. Only one case of father-to-daughter transmission has been previously reported. We report a second case of father-to-daughter transmission of IP. Chromosomal analysis of blood and fibroblasts from the father failed to provide evidence of genetic mosaicism.

Adult↗
PubMed1991

Unique phenotype associated with a pericentric inversion of chromosome 6 in three generations.

We observed a pericentric inversion of chromosome 6 in three generations of one family. Carriers had several phenotypic alterations including congenital cataracts, hearing loss, dental anomalies, ear anomalies, premature graying, unilateral strabismus, coloboma, and mild mental retardation. These manifestations may all be explained by a failure or delay in development of tissues derived from neural crest cells and are similar to these seen in the Rieger syndrome. The description of this family extends the known phenotypic abnormalities associated with alterations of chromosome 6.

Abnormalities, Multiple↗
PubMed1991

Characterization of seven DA/DAPI-positive bisatellited marker chromosomes by in situ hybridization.

Seven dicentric bisatellited marker chromosomes, ascertained at amniocentesis, chorionic villus sampling, and in blood from an abnormal liveborn were characterized cytogenetically. All seven markers demonstrated brilliant bands by the DA/DAPI technique corresponding to C-band positive regions. Although some dicentric DA/DAPI-positive bisatellited markers have been identified as inverted duplicated 15s, recent literature has suggested that DA/DAPI lacks specificity for chromosome 15. Our evaluation of DA/DAPI-positive bisatellited marker chromosomes by in situ hybridization shows that some originate from chromosome 15 whereas DA/DAPI negative bisatellited markers may not be derived from 15. The morphological variations noted in our studies are discussed with respect to nomenclature.

Amniocentesis↗
PubMed1991

Clinical management issues in males with sex chromosomal mosaicism and discordant phenotype/sex chromosomal patterns.

The recent availability of Y DNA probes has made it possible to identify two forms of 46,XX male syndrome: Y DNA positive and Y DNA negative. The Y DNA positive male results from a X;Y translocation with a low recurrence risk; the Y DNA negative males are due to a mutation with a high recurrence risk. 46,XX males and mosaic forms are phenotypically indistinguishable. A review of the case histories for 11 individuals indicates that affected males have highly variable genital and nongenital phenotypes. Physical findings may be clearly apparent or nonexistent. With the exception of external genitalia, the basis for this variability is unknown. It may be related to differences in Y chromatin expression as the result of variable inactivation of the X chromosomes, or to the existence of minor deletions or point mutations secondary to an exchange of genetic material. Common and uncommon clinical problems in these individuals require evaluation and follow-up care that is provided through a cooperative, interdisciplinary approach.

Adolescent↗
PubMed1990

Trisomy 13: a new recurring chromosome abnormality in acute leukemia.

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.

Acute Disease↗
PubMed1990

Trisomy 12 mosaicism in phenotypically normal fetuses following prenatal detection.

We report three cases of amniocentesis in which mosaicism for trisomy 12 was detected in two or more independent cultures. The parents elected to terminate the pregnancy in all three cases. Follow-up studies in two of the cases confirmed the mosaicism in fetal tissues (in subcutaneous tissue in one case; in fetal lung in the other), but not in blood. No fetal anomalies were evident by ultrasound or at autopsy. These results along with other reported cases demonstrate the difficulty in counselling for mosaic trisomy 12.

Adult↗
PubMed1990

Variability in expression of common fragile sites: in search of a new criterion.

Fragile sites are nonrandom, heritable sites on chromosomes that can be induced to form gaps, breaks, and rearrangements under specific conditions. There is currently no established criterion to define a common fragile site. We applied seven published criteria to our data from three groups of subjects: (1) three pairs of like-sexed twins, (2) four unaffected von Hippel-Lindau (VHL) family members, and (3) six patients affected with VHL disease. Substantial differences were present in the numbers of sites considered positive by these criteria. While some of this variability can be attributed to technical factors, our data illustrate the problems in comparing results from different studies to assess the significance of fragile sites. A recently published criterion is based upon the Poisson distribution. We found this criterion to be flawed in its presentation, and furthermore, the Poisson distribution did not provide an adequate approximation to our data. We propose here an alternative approach based upon the negative binomial distribution.

Binomial Distribution↗
PubMed1990

Localization of the Miller-Dieker critical region is proximal to locus D17S34 (p144D6) in 17p13.3.

A child with normal growth and development and the abnormal karyotype 46,XY,17ps, was analyzed using molecular probes localized to 17p13. The results indicated the presence of two copies of the probes YNZ22.1 (D17S5) and YNH37.3 (D17S28), previously shown to be deleted in all Miller-Dieker (MDS) patients studied. However, the patient was hemizygous for probe p144D6 (D17S34), which is absent in approximately 75% of the MDS patients. As the patient is active at 9 months of age, with no clinical signs of MDS, the results confirm that the absence of locus D17S34 does not lead to the phenotypic expression of MDS. Furthermore, this deletion should assist in defining the distal limits of this contiguous gene syndrome.

Abnormalities, Multiple↗
PubMed1989

Cytogenetic abnormalities in tumors of patients with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that causes the development of benign and malignant tumors in several organ systems. Tumors causing significant morbidity include retinal angioma, cerebellar hemangioblastoma (CH), renal cell carcinoma (RCC), and pheochromocytoma (Pheo). Cytogenetic studies of tumors in VHL patients are rare. Cytogenetic findings in tumors from 12 patients with VHL disease, including four RCCs, three CHs, and five Pheos are presented. Three of the four RCC cases were abnormal. Monosomy 3 or a deletion of 3p was present in all three abnormal cases. Complete or partial trisomy of chromosome 5 was present in two cases. A deletion of 14q, trisomy 7, and a missing Y were each observed in one case. These findings indicate that a deletion of 3p may be a primary cytogenetic change in RCCs associated with VHL disease in addition to playing a role in sporadic RCC. Duplications of 5q and deletions of 14q may be important secondary changes in the progression of the malignant phenotype. No visible cytogenetic abnormalities were observed in the three CHs, or in four of the Pheos. One of the five Pheos was found to exhibit mosaic trisomy 7; its significance is unclear at the present time.

Adrenal Gland Neoplasms↗
PubMed1989

Fragile site expression in families with von Hippel-Lindau disease.

Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that predisposes to diverse tumors including renal cell carcinoma. Six affected and four unaffected subjects from five families were studied to determine the frequency of fragile site expression. Peripheral lymphocyte cultures from each subject were treated with low folate, 5-fluorodeoxyuridine (FUdR), and FUdR plus caffeine for fragile site induction. A site was considered to be fragile if it was expressed at least two times in half of the affected or unaffected subjects. Of the established sites, four were expressed in the unaffected group (3p14, 6p22, 8q22, and Xp22) and six were expressed in the affected group (3p14, 4q31, 5q31, 7q32, Xp22, and Xq22). Only 3p14 and Xp22 were expressed in both groups. There were four new sites: three (3q26, 6p21, 7p15) in the unaffected group and one (16q24) in the affected group. The 3p14 site was expressed twice as frequently in affected versus unaffected subjects. This finding is of interest because of reports of the involvement of 3p14 in hereditary renal cell carcinoma and in VHL.

Adult↗
PubMed1989

8;21 translocation in acute nonlymphocytic leukemia. Occurrence in M1 and M2 FAB subtypes.

Ten patients with acute nonlymphocytic leukemia (ANLL) and the 8;21 chromosome translocation were observed over an eight-year period. The mean age of the patients was 31, and nine achieved a complete remission. Six were classified as ANLL-M2, three as ANLL-M1, and one as borderline M1/M2. A missing sex chromosome was also observed in four of the ANLL-M2 patients but not in the three M1 patients. An increased number of dyspoietic myeloid cells and/or basophils was present in four patients in day 14 or 21 marrows after induction therapy, but this feature did not appear to adversely affect prognosis. Previous reports have stated that t(8;21) occurs almost exclusively in ANLL-M2. However, by revised French-American-British criteria for classification of ANLL, the M1 subtype may also be observed with significant frequency.

Adolescent↗