Background Karyotyping has been the gold standard for prenatal chromosome analysis. The resolution should be higher by chromosome microarray analysis (CMA). The challenge lies in recognizing benign and pathogenic or clinically significant... more
Background Karyotyping has been the gold standard for prenatal chromosome analysis. The resolution should be higher by chromosome microarray analysis (CMA). The challenge lies in recognizing benign and pathogenic or clinically significant copy number variations (pCNV) and variations of unknown significance (VOUS). The aim was to evaluate the diagnostic yield and clinical utility of CMA, to stratify the CMA results in various prenatal referral groups and to accumulate Indian data of pCNVs and VOUS for further interpretation to assist defined genetic counseling. Methods Karyotyping and CMA were performed on consecutive referrals of 370 prenatal samples of amniotic fluid ( n = 274) and chorionic villi ( n = 96) from Indian pregnant women with high maternal age ( n = 23), biochemical screen positive ( n = 61), previous child abnormal ( n = 59), abnormal fetal ultrasound ( n = 205) and heterozygous parents ( n = 22). Results and Conclusion The overall diagnostic yield of abnormal ...
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BackgroundPartial Trisomy 11q syndrome (or Duplication 11q) has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD). Deletion 1q44 (or Monosomy 1q44) is a well-defined syndrome,... more
BackgroundPartial Trisomy 11q syndrome (or Duplication 11q) has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD). Deletion 1q44 (or Monosomy 1q44) is a well-defined syndrome, but there is controversy about the genes lying in 1q44 region, responsible for agenesis of the corpus callosum. We report a female child with the rare Partial Trisomy 11q syndrome and Deletion 1q44 syndrome. The genomic imbalance in the proband was used for molecular characterization of the critical genes in 1q44 region for agenesis of corpus callosum. Some genes in 11q14q25 may be responsible for laryngomalacia.ResultsWe report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1)t(1;11)(q44;q14)pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11)(q44;q14). SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter.ConclusionLaryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region.
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4725 Introduction Biological subtypes of pediatric Acute Lymphoblastic Leukemia (ALL) have emerged as the most important prognostic factor for response to treatment. Since the genetic subtypes differ according to ethnic groups, it becomes... more
4725 Introduction Biological subtypes of pediatric Acute Lymphoblastic Leukemia (ALL) have emerged as the most important prognostic factor for response to treatment. Since the genetic subtypes differ according to ethnic groups, it becomes important to consider this factor while comparing survival between different geographic areas. We describe the relative frequency of genetic subtypes and the effect on survival and duration of first remission in patients diagnosed with ALL from a single centre in India. Patients and Methods Bone marrow karyotyping and fluorescent in-situ hybridization (FISH) studies for BCR ABL and TEL AML1 were performed on 98 children diagnosed with ALL at Sir Ganga Ram Hospital, Delhi between Jan 2005 and June 2009. During this period of 54 months, a total of 176 patients were diagnosed with ALL. Cytogenetic analysis could be done only in 98 patients. It could not be done in others due to monetary constraints. 27 did not have adequate metaphase for karyotyping. ...
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Background: Prevention of genetic disorders in the family is gaining significance because of the burden of these untreatable and devastating disorders. Sir Ganga Ram Hospital (SGRH) has been at the forefront for prenatal diagnosis (PND)... more
Background: Prevention of genetic disorders in the family is gaining significance because of the burden of these untreatable and devastating disorders. Sir Ganga Ram Hospital (SGRH) has been at the forefront for prenatal diagnosis (PND) in India for the last 2 decades. Aims and objectives: Evaluation of pregnant women for prenatal diagnosis in year 2017, and comparison with the centre's historical 5-year data published in 2003. Material and methods: Pregnant women attending genetic clinics at SGRH and prenatal samples received from elsewhere were enrolled. Cytogenetic, molecular, biochemical and non-invasive methods were utilized for PND. Results: Among 3351 pregnant women from SGRH, 2530 presented with obstetric indications, and 821 women had a background family history. In cytogenetic laboratory, 706 prenatal samples from SGRH and 553 samples from elsewhere were analyzed. Additional 623 women opted for Non-invasive prenatal test (NIPT) for aneuploidies. In molecular genetics laboratory, 733 prenatal samples were analyzed. Highlights in the study included the introduction of NIPT, and other major advances-chromosomal micro-arrays and next-generation sequencing enabling PND in 130 and 20 cases, respectively. NIPT detected 10 cases of aneuploidy, with 10% false positivity in 623 women. Comparison with 5-year data from SGRH revealed a 6e10 fold rise in number of PNDs being performed, and addition of newer indications, materialized by newer methods of NGS and CMAs. Conclusion: Advanced genetic testing methodologies like NIPT, NGS and CMA are rapidly changing the scenario of prenatal diagnosis in our country, which is reflected in our data of last one year.
Noninvasive prenatal testing (NIPT) is a reliable screening method for fetal aneuploidy detection of trisomy 18, 13, 21 along with few sex chromosome abnormalities monosomy X, XXX, XXY (Klinefelter), XYY (Jacob) syndromes and certain... more
Noninvasive prenatal testing (NIPT) is a reliable screening method for fetal aneuploidy detection of trisomy 18, 13, 21 along with few sex chromosome abnormalities monosomy X, XXX, XXY (Klinefelter), XYY (Jacob) syndromes and certain microdeletions which include cri-du-chat, DiGeorge, 1p36, Angelman, and Prader-Willi syndromes in comparison to the available screening methods. Prenatal screening of Turners syndrome is possible by ultrasound in certain conditions only. Recently benefits of early detection and treatment of Turners syndrome has been emphasized, enforcing on accurate and early screening prenatally. The current case emphasizes on the reliability of NIPT testing which comes with an advantage of early screening. A 24-year-old primi gravida was referred for NIPT as she tested for high risk on biochemical screening. The Panorama™ NIPT results showed low risk for trisomies, 21, 18, and 13 but high risk of monosomy X and was advised confirmatory amniocentesis. The fluorescence ...
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5p deletion syndrome or Cri du Chat syndrome is a autosomal deletion syndrome, caused by the de novo deletion of chromosome 5p in the majority of the cases. Clinical features include developmental delay, microcephaly, subtle facial... more
5p deletion syndrome or Cri du Chat syndrome is a autosomal deletion syndrome, caused by the de novo deletion of chromosome 5p in the majority of the cases. Clinical features include developmental delay, microcephaly, subtle facial dysmorphism and high-pitched cry. With the advent of newer techniques such as multiplex ligation-dependent probe amplification, rapid diagnosis is possible and chromosomal microarray helps in accurate delineation of the breakpoints. In this study, we characterized probands from two Indian families who had duplication of another chromosome in addition to deletion of 5p region. In the first family, two females of 3 and 5 yr of age had deletion of 5p15.33p15.2 (14.7 Mb) and duplication of 8q24.21q24.3 (15.4 Mb). Proband in the second family was a 2-year-old female and had deletion of 5p15.33p14.3 (22.55 Mb) along with duplication of 12p13.33p13.31 (7.7 Mb). In both the families, father was balanced translocation carrier of the chromosomes involved. Patients ...
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The utility of fetal autopsy to corroborate antenatal ultrasound findings and to aid genetic counseling is well known. However, the ability to identify an underlying cause for the common indications for which it is performed is not well... more
The utility of fetal autopsy to corroborate antenatal ultrasound findings and to aid genetic counseling is well known. However, the ability to identify an underlying cause for the common indications for which it is performed is not well studied. This study aimed to determine if the diagnostic yield of fetal autopsy in identifying the underlying cause is determined by the indication of the autopsy. Five groups of fetuses were defined based on the indication for the autopsy performed in 903 cases: (i) malformations, (ii) intrauterine death (IUD), (iii) cystic hygroma and hydrops fetalis, (iv) isolated abnormalities of amniotic fluid, and (v) intrauterine growth restriction (IUGR). The highest diagnostic yield was in fetuses with isolated abnormalities of amniotic fluid (77%), followed by those with IUGR (75%), with IUD (69.6%), those in group five (55.2%) and lowest (45%) in fetuses with malformations (P < 0.001). A cause was identified in 77.8% fetuses with multiple malformations ...
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We report an unusual case of bi-lineal mixed-phenotype acute leukemia (T/Myeloid, NOS) with complex cytogenetic abnormalities in a 2-year-old boy. Despite attaining complete remission with therapy, he succumbed to status epilepticus... more
We report an unusual case of bi-lineal mixed-phenotype acute leukemia (T/Myeloid, NOS) with complex cytogenetic abnormalities in a 2-year-old boy. Despite attaining complete remission with therapy, he succumbed to status epilepticus following febrile illness. Flow cytometry represents the current standard of care for the diagnosis of this malignancy and the approach adopted in our case is discussed.
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1. Pediatr Hematol Oncol. 2011 Aug 29. [Epub ahead of print] Pediatric Acute Myeloid Leukemia: Final Frontier for Pediatric Oncologists in Developing World. Yadav SP, Ramzan M, Lall M, Sachdeva A. 1Pediatric Hematology ...
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Abstract. The experiences in genetic counseling and prenatal diagnosis at a tertiary genetic center in India are described. Of 3500 subjects provided genetic counseling 28.7% were for prenatal diagnosis, 13.7% for mental retardation +... more
Abstract. The experiences in genetic counseling and prenatal diagnosis at a tertiary genetic center in India are described. Of 3500 subjects provided genetic counseling 28.7% were for prenatal diagnosis, 13.7% for mental retardation + malformations, 11.5% for thalassemia, ...