Papers by Udayakumar Achandira
American journal of hematology, Mar 4, 2024
Journal of Genetic Counseling, Sep 19, 2014
The incidence of congenital anomalies and/or genetic disorders in the Omani population has reache... more The incidence of congenital anomalies and/or genetic disorders in the Omani population has reached figures greater than double the global statistics. Preference for consanguineous unions together with the fact that termination of pregnancy in Muslim communities are largely avoided, have been highlighted as contributing factors. This overview identifies a third significant aspect contributing to the elevated rate of genetic disorders in the Omani population. Namely, a lack of services that are able to offer termination of pregnancy for severe congenital anomalies, to requesting parents. In this report we select an unusual case of a family at risk for two distinct genetic disorders-6q micro-deletion and unbalanced products of conception attributed to a balanced parental translocation involving chromosome 3 and 13, to portray and examine the current situation faced by Omani couples interested in prenatal diagnosis for termination of pregnancy. Additional challenges and pitfalls to developing a prenatal diagnostic service as part of the genetic service in Oman are discussed.
Follicular Dendritic Cell Sarcoma: Cytogenetics and Pathological Findings Abstract Follicular Den... more Follicular Dendritic Cell Sarcoma: Cytogenetics and Pathological Findings Abstract Follicular Dendritic Cell Sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation that is further complicated by difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence or metastasis. Unlike other soft tissue sarcomas, cytogenetic studies are very limited in FDCS. Although no specific chromosomal marker is established yet, complex aberrations, different ploidy types are documented. We present a case with ultra-structural, immunophenotypical and histological features. The karyotypic findings were different from those reported in literature. Keywords: Chromosomal aberrations; Cytogenetics; FDCS; Fine needle aspiration;Follicular dendritic cell sarcoma;karyotype
The duplication of short arm of chromosome 7 as de novo is extremely rare. Its phenotype spectrum... more The duplication of short arm of chromosome 7 as de novo is extremely rare. Its phenotype spectrum varies depending on the region of duplication. We report a case of de novo duplication of chromosomal region 7p21.1p22.2 in a 3-year-old male child with autism. The patient was diagnosed with craniofacial dysmorphism, global developmental delay, hypotonia and bilateral cryptorchidism. This was detected by conventional G-banded karyotype/FISH and confirmed by array CGH. To the best of our knowledge, this is the first report of chromosomal region 7p21.1 involvement in a patient with autism spectrum disorder, showing features of 7p duplication phenotype. Identifying genes in the duplicated region involved using molecular techniques would promote characterize the phenotype and associated disease condition. Duplication of 7p have been reported previously and the region/size varies among patients. The common features were craniofacial anomalies, large fontanelle, dysmorphism, psychomotor delay,5 and hypotonia was the most common complication observed. Review showed that 50% of 7p duplications were the result of balanced reciprocal translocation carriers. It could be an entire duplication of 7p in few or smaller but more terminal 7p in others.3 Arens et al reported complete 7p trisomy (without the involvement of any other chromosomes) in two patients.6 Similar diagnosis has been pursued in five other patients. 4,7 Many phenotypic features common of 7p duplication syndrome were present in our patient (Table I) as described in earlier reviews. 3,6,8 Noticeably, our patient did not have any cardiovascular abnormalities and thus showed better prognosis as compared to early deaths observed in previous reports. 3,6,8 Although evidences suggest that most 7p duplications occur due to malsegregation of parental balanced translocations or due to abnormal recombination of parental chromosome inversions; 2,3 few rare cases however result from de novo partial 7p direct duplication. The critical region however is assigned to 7p15 to pter for physical and mental abnormalities,2 and 7p21 for craniofacial dysmorphism. 3,9 Both these patient groups had many specific features in common. The range of severity might depend on the size and genes involved. It is suggested that genes GLI3(OMIM 165240; 7p13, HOXA13(OMIM 142959;7p15-7p14.2), TWIST (OMIM 601622; 7p21), CRS1(OMIM 123100; 7p21.3-7p21.2) and MEOX2 (OMIM 600535; 7p22.1-7p21.3) are associated with phenotype of 7p syndromes.1 A patient who had a microduplication at 7p22.1(1.7Mb) showed all the common craniofacial features and cryptorchidism, but global developmental delay and hypotonia was not observed,10 Although the region 7p22.1 contains 27 genes, 13 of which are OMIM-annotated, only one gene ACTB was the commonly observed in both their and our patient; which is likely to be the causative factor for features like hypotonia, global developmental delay and cryptorchidism. The databases like ODD and LOVD are useful for routine consultation in array diagnostics. Our patient who had a larger duplication (16.5Mb) showed global developmental delay and hypotonia in addition to craniofacial dysmorphism. The segmental size of duplication in our patient is relatively larger (16.5Mb) as compared to a few earlier reports,11 (Table I). An interesting clinical observation in our patient was its association with the ASD. Earlier, two reports had their 7p duplication associated with this disorder. One report is of an inverted duplication 7p14.1p11.2in an adult, 4 who lacked many characteristic features of the described 7p dup syndrome. This could possibly support that the critical region is distal. He was normocephalic, had normal milestones, meatal stenosis, bilateral esotropia and mild scoliosis. The other report was of autistic first cousins who carry two microduplications concordant with disease, one of whom had a tandem duplication on 7p21 that replicates part of the neurexophilin 1 and islet cell autoantigen 1 genes.12 Our patient was a child with direct duplication showing microcephalic and delayed milestones. None of the other features were present. But both these patients showed the autistic phenotype/behavioral features in common.The duplication was more proximal in previous case whereas it is distal in ours. The region 7p21.1 to 7p22.2 observed in our patient has been suggested to be the critical region for the manifestations of the 7p duplication phenotype. This region of 7p contains the OMIM Morbid gene TWIST1 (OMIM*606122), duplications of which are thought to be the cause of the large fontanelles in these patients,13 and hence it is likely to be the cause of our patients clinical phenotype. The duplication region of our patient encompasses the whole of TWIST1,ICA1 (OMIM*147625) and NXPH1 (OMIM*604639) genes. These genes however are not directly disrupted by the breakpoints of this duplication. The array CGH analysis could not determine whether this duplication might have an effect…
Qatar Foundation Annual Research Forum Volume 2013 Issue 1, 2013
Monosomy 18p syndrome is a rare, 50-year-old chromosomal disorder with varying phenotypical clini... more Monosomy 18p syndrome is a rare, 50-year-old chromosomal disorder with varying phenotypical clinical manifestations. Dysmorphism, growth delay, delayed speech and mental retardation are a few common features observed. The cytogenetic findings also vary in each case. It may occur just as a pure deletion of entire 18p arm or as deletion of partial 18p arm, if involved in a translocation with other chromosomes. It may either occur solely or along with structurally altered other chromosome 18, as a ring or an isochromosome. Studies suggest genotype-phenotype correlation, in relation to the locus of chromosomal breakpoint present on 18p with its clinical presentation. Often, the clinical presentation of this syndrome overlaps with other syndromes. Hence, establishing a cytogentic diagnosis is very crucial for precise management and follow up. Although there are earlier reports of cases with deletion of 18p alone, very few cases are reported with additional abnormalities particularly i(18q). There was only a single case report of a mosaic with del 18p/i(18q) three decades ago. We present here, the second report of a rare case with de novo mosaic - deletion 18p with isochromosome 18q, in a boy born to a consanguineous Arabic Omani couple with review of the literature.
Qatar Foundation Annual Research Conference Proceedings Volume 2016 Issue 1
Qatar Foundation Annual Research Conference Proceedings Volume 2016 Issue 1
Sultan Qaboos University Medical Journal, 2015
Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious pre... more Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation further complicated by the difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence and metastasis. Unlike other soft tissue sarcomas or histiocytic and dendritic cell neoplasms, cytogenetic studies are very limited in FDCS cases. Although no specific chromosomal marker has yet been established, complex aberrations and different ploidy types have been documented. We report the case of a 39-year-old woman with FDCS who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in February 2013. Ultrastructural, immunophenotypical and histological findings are reported. In addition, karyotypic findings showed deletions of the chromosomes 1p, 3q, 6q, 7q, 8q and 11q. To the best of the authors' knowledge, these have not been reported previously in this tumour. Techniques such as spectral karyotyping may help to better characterise chromosomal abnormalities in this type of tumour.
Qatar Foundation Annual Research Forum Proceedings, 2013
Case Reports, 2009
This report describes a case of acute lymphoblastic leukaemia in which isochromosome 9q (i(9q)) w... more This report describes a case of acute lymphoblastic leukaemia in which isochromosome 9q (i(9q)) was the sole acquired cytogenetic abnormality. The Immunophenotype showed positivity for CD3, CD4, CD5, CD7, CD8, CD10, CD71, CD117 and TdT, consistent with T cell acute lymphoblastic leukaemia (ALL). The chromosomal analysis of bone marrow showed 46,XY,i(9)(q10) in all the metaphases analysed. The bone marrow morphology was ALL-L2 as per the French-American-British criteria. Isochromosomes are rare chromosomal abnormalities in childhood ALL and the effect of i(9q) is not well established. The patient's good response to therapy with normal cytogenetics within a month of induction, and disease-free survival after bone marrow transplant are indicative of a good prognosis in such cases.
Journal of Genetic Counseling, 2015
Leukemia & Lymphoma, 2014
Cancer Genetics and Cytogenetics, 2002
We report cytogenetic findings from fine-needle aspiration samples of two synovial sarcoma patien... more We report cytogenetic findings from fine-needle aspiration samples of two synovial sarcoma patients. The cases are of interest because (1) one case is of a rare site (submandibular region) of the head and neck, and (2) the other is a patient with synovial sarcoma of the toe showing additional cytogenetic abnormalities along with t(X;18). The literature of this tumor is reviewed.
Cancer Genetics and Cytogenetics, 2007
Chromosome aberrations observed at diagnosis are considered to be the most valuable prognostic fa... more Chromosome aberrations observed at diagnosis are considered to be the most valuable prognostic factors in acute myeloid leukemia (AML). Some specific aberrations vary in frequency among different geographical areas and ethnic groups. There are only limited studies on the role of such variability in AML patients. Here, we report the results of a cytogenetic study on 63 ethnic Omani patients with de novo AML: 18 children (<16 years) and 45 adults. By sex, 41 were male and 22 female; median age at diagnosis was 25 years. The morphological diagnosis was based on the FrencheAmericaneBritish (FAB) WHO criteria. Chromosome abnormalities were present in 39 of 63 patients (62% overall, or 44% for adults and 18% for children). Karyotypes with a sole abnormality accounted for 20 of 63 patients (32%). Chromosome abnormalities were more common in patients with the FAB-M2 subtype (15 of 22; 68%), which was also the most frequent subtype observed (22 of 63; 35%). Among the normal karyotypes (24 of 63; 38%), M2 subtype was the also most frequent (7 of 24; 29%), followed by M4 (4 of 24; 17%). Balanced translocations, t(8;21) and t(15;17) were observed in 7 of 63 (11%) and 6 of 63 (10%), respectively. Inv(16) was seen in 2 of 63 (3%). Trisomy 8 was the most frequent numerical anomaly, found in 7 of 63 (11%). Monosomy 7 was seen in 3 of 63 (5%). The patterns in our study were similar to those reported from Saudi Arabia and Kuwait, but the frequency of abnormalities varied. Our population differed morphologically, with the M2 subtype as most common, whereas M4 and M3 were more commonly in those reports. A comparison of our findings was made with other geographic and ethnic groups. This is the first systematic cytogenetic study of an ethnic Omani population.
Cancer Genetics and Cytogenetics, 2002
ABSTRACT
Archives of Medical Research, 2007
Background. Chromosomal abnormalities have important diagnostic and prognostic significance in ac... more Background. Chromosomal abnormalities have important diagnostic and prognostic significance in acute lymphoblastic leukemia (ALL). The purpose of this study was to define and classify the frequency and type of chromosomal abnormalities among newly diagnosed children with ALL and compare the results with those reported from other geographical regions of the world. Methods. Bone marrow chromosomal studies with GTG banding were performed in untreated ALL pediatric patients aged from 7 days to 14 years. Results. Among Omani children examined with ALL, 47 (81%) patients yielded results, with 26 (55.3%) showing an abnormal karyotype [10 (21.3%) pseudodiploid, 2 (4.3%) hypodiploid and 14 (29.7%) hyperdiploidy] and 21 (44.6%) had normal diploidy. Structural abnormalities were observed in 16 (34%), of which 11 (23.4%) cases were translocations, the most frequent being t(9;22) observed in three (6.4%) of our patients. Uncommon translocations such as t(9;15)(p11;q10), t(3;6)(p12;q11), t(1;6)(?31;?q23), t(1;19)(q12;q12), der(18)t(12;18)(q11;p11), and other structural aberrations add(2)(q22), add(6)(q16), add(18)(q22), add(14)(q32) along with deletions del(10)(q22), del(12)(p11), del(12)(p12), del(18)(q11) were also observed. Conclusions. The study showed a good correlation and concordance between the ploidy distribution by cytogenetics and flow cytometry. The patterns of chromosomal anomalies in our patients showed some variations in the frequency of aberrations reported. It is therefore necessary that newer techniques like fluorescence in situ hybridization (FISH) along with reverse transcriptase polymerase chain reaction (RT-PCR) and spectral karyotyping will help us identify chromosomal aberrations not detected by conventional cytogenetic methods in the near future. To our knowledge, this is the first report from the Middle East of a cytogenetic study on childhood ALL. Ó 2007 IMSS.
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Papers by Udayakumar Achandira