Madhulika Kabra

AIIMS Bhopal All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India

Are you Madhulika Kabra?

Claim your profile

Publications (280)600.88 Total impact

  • Madhulika Kabra · Neerja Gupta

    No preview · Article · Feb 2016 · Indian pediatrics
  • [Show abstract] [Hide abstract]
    ABSTRACT: Smith-Magenis syndrome is a well delineated microdeletion syndrome with characteristic facial and behavioral phenotype. With the availability of the multi-targeted molecular cytogenetic techniques like Multiplex Ligation Probe Amplification and cytogenetic microarray, the cases are diagnosed even without clinical suspicion. Here, the authors present clinical features of nine Indian cases of Smith-Magenis syndrome. Characteristic facial phenotype including tented upper lip, broad forehead, midface hypoplasia, short philtrum and upslant of palpebral fissure is obvious in the photographs. The behavioral variations were seen in some of the cases but were not the presenting features. The characteristic facial phenotype can be an important clinical guide to the diagnosis.
    No preview · Article · Dec 2015 · The Indian Journal of Pediatrics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Multicentric osteolysis nodulosis and arthropathy (MONA) is an infrequently described autosomal recessive skeletal dysplasia characterized by progressive osteolysis and arthropathy. Inactivating mutations in MMP2, encoding matrix metalloproteinase-2, are known to cause this disorder. Fifteen families with mutations in MMP2 have been reported in literature. In this study we screened thirteen individuals from eleven families for MMP2 mutations and identified eight mutations (five novel and three known variants). We characterize the clinical, radiographic and molecular findings in all individuals with molecularly proven MONA from the present cohort and previous reports, and provide a comprehensive review of the MMP2 related disorders. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Nov 2015 · American Journal of Medical Genetics Part A
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The generation of disease-specific induced pluripotent stem cells (iPSCs) holds a great promise for understanding disease mechanisms and for drug screening. Recently, patient-derived iPSCs, containing identical genetic anomalies of the patient, have offered a breakthrough approach to studying Duchenne muscular dystrophy (DMD), a fatal disease caused by the mutation in the dystrophin gene. However, development of scalable and high fidelity DMD-iPSCs is hampered by low reprogramming efficiency, the addition of expensive growth factors and slow kinetics of disease-specific fibroblasts. Here, we show an efficient generation of DMD-iPSCs on bFGF secreting human foreskin fibroblast feeders (I-HFF) by employing single polycistronic lentiviral vector for delivering of transcription factors to DMD patient-specific fibroblast cells. Using this method, DMD-iPSCs generated on I-HFF feeders displayed pluripotent characteristics and disease genotype with improved reprogramming efficiency and kinetics over to mouse feeders. Moreover, we were able to maintain disease-specific iPSCs without additional supplementation of bFGF on I-HFF feeders. Our findings offer improvements in the generation of DMD-iPSCs and will facilitate in understanding of pathological mechanisms and screening of safer drugs for clinical intervention. Key Words: Duchenne Muscular Dystrophy, Reprogramming, Induced pluripotent Stem Cells, Immortalized Human Feeder, Basic Fibroblast Growth Factor, Stem Cell Cassette.
    Full-text · Article · Nov 2015 · PLoS Currents
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Children with cystic fibrosis may have a deficiency of micronutrients, including zinc, which may affect their susceptibility to infections. There is a paucity of data on zinc supplementation among children with cystic fibrosis. We hypothesized that a pharmacologic dose of zinc administered daily for 12 months would reduce the need for antibiotics by 50%. Methods: This double-blind randomized placebo-controlled trial was conducted among children with cystic fibrosis to assess the effect of zinc supplementation on the need for antibiotics and pulmonary function tests. The children, age 5-15 y, of either sex, received either 30-mg zinc tablets or similar looking placebo tablets daily in addition to standard care. They were followed up every month for a period of 12 months and whenever they had pulmonary exacerbations. Their serum zinc was estimated at baseline and at 12 months of enrollment. During each visit, the children underwent a pulmonary function test and sputum culture. Results: Of a total of 43 children screened, 40 were enrolled, and of them, 37 completed the study. The median (interquartile range) number of days of the administration of antibiotics over 12 months of follow-up among the children receiving zinc was 42 (14-97) d. In the placebo group, it was 38 (15-70) d (P = .79). There were no significant differences in the percent-of-predicted FEV1 or change in FEV1 values at 12 months (P = .44). The number of children in whose respiratory specimens Pseudomonas was isolated was similar for the 2 groups at different time intervals. The adverse events reported were similar in the 2 groups. Conclusion: We did not find any significant difference in the need for antibiotics, pulmonary function tests, hospitalization, colonization with Pseudomonas, or the need for antibiotics for children with cystic fibrosis receiving zinc supplementation of 30 mg/d.
    No preview · Article · Oct 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Williams-Beuren syndrome (WBS) or Williams syndrome (OMIM 194050) is a multisystem disorder manifested by neurodevelopmental delay and is caused by a hemizygous deletion of ∼1.5-1.8 Mb in the 7q11.23 region. Clinical features include cardiovascular anomalies (mainly supravalvular aortic stenosis), peripheral pulmonary stenosis, distinctive facies, intellectual disability (usually mild), unique personality characteristics, and growth and endocrine abnormalities. Clinical diagnostic criteria are available for WBS; however, the mainstay of diagnosis is the detection of the contiguous gene deletion. Although FISH remains the most widely used laboratory test, the diagnosis can also be established by means of qPCR, MLPA, microsatellite marker analysis, and chromosomal microarray (CMA). We evaluated the utility of MLPA to detect deletion/duplication in the 7q11.23 region in 43 patients suspected to have WBS using MLPA kits for microdeletion syndromes. A hemizygous deletion in the 7q11.23 region was found in 41 (95.3%) patients using MLPA. One patient had an atypical deletion detected by CMA. During the initial period of this study, the results of 12 patients tested by MLPA were also confirmed by FISH. Compared to FISH and CMA, MLPA is a cheaper, high-throughput, less labor-intensive and less time-consuming technique for the diagnosis of WBS. Although CMA is expensive and labor-intensive, its effectiveness is demonstrated to detect an atypical deletion and to delineate the breakpoints.
    No preview · Article · Sep 2015 · Cytogenetic and Genome Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chanarin Dorfman Syndrome (CDS) is a very rare neutral lipid metabolism disorder with multisystem involvement. It is inherited as an autosomal recessive manner. It is characterized with congenital ichthyosiform erythroderma and involvement of liver, muscle, and central nervous system. Demonstration of lipid vacuoles in neutrophils from peripheral blood smears in patients with ichthyosiform erythroderma leads to the diagnosis. We report a novel ABHD5 truncating variant in a twenty nine month old female child, who presented with icthyosiform erythroderma.
    No preview · Article · Sep 2015 · Gene
  • Source

    Full-text · Article · May 2015 · American Journal of Medical Genetics Part A
  • [Show abstract] [Hide abstract]
    ABSTRACT: GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-D-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of alleles frequency in our cohort of patients, suggesting these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, β-domain 1 and β-domain 2. In silico sequence and structure analysis of GLB1 reveals that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Apr 2015 · Gene
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hydatidiform mole (HM) is an aberrant human pregnancy with abnormal embryonic development and excessive proliferation of the trophoblast. Recessive mutations in NLRP7 are responsible for recurrent HM (RHM). Women with recessive NLRP7 mutations fail to have normal pregnancies from spontaneous conceptions with the exception of three out of 131 reported patients. Because there is no treatment for RHM and maternal-effect genes are needed in the oocytes to sustain normal embryonic development until the activation of the embryonic genome, one patient with recessive NLRP7 mutations tried ovum donation and achieved a successful pregnancy. This study reports three additional live births from donated ova to two patients with recessive NLRP7 mutations. The occurrence of two live births from spontaneous conceptions to two other patients is also reported. The reproductive outcomes and mutations of all reported patients were reviewed and it was found that live births are associated with some missense mutations expected to have mild functional consequences on the protein. The data support a previous observation that ovum donation appears the best management option for these patients to achieve normal pregnancies and provide an explanation for the rare occurrence of live births from natural spontaneous conceptions in patients with two NLRP7 mutations. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · Reproductive biomedicine online
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of our study was to examine the association of low pregnancy-associated plasma protein-A (PAPP-A) with adverse pregnancy outcome. A total of 1640 consecutive pregnant women between 9(+5) and 13(+6) weeks of pregnancy were recruited. One hundred and thirty women with PAPP-A levels < 0.4 multiple of median were followed till delivery and the outcome information was obtained for fetal loss, birthweight, growth restriction, preterm birth, reduced liquor and development of pre-eclampsia. During the study period, 130 (7.92%) women had low PAPP-A and were considered as cases and 200 women with normal PAPP-A were controls. Intrauterine growth restriction was observed in 28 (21.54%) cases as compared to 10 (5%) controls. Pre-eclampsia presented in 24 (18.46%) cases and in 18 (9%) controls. Twenty (15.38%) cases had preterm delivery compared to 12 (6%) controls. Fifty-six (43.08%) cases delivered low-birthweight babies compared to 22 (11%) controls. Thus, the incidence of intrauterine growth restriction, preterm birth and low birthweight was significantly more in the cases as compared to the control group. PAPP-A is a valuable analyte for predicting risk of adverse pregnancy outcome and women with low serum PAPP-A levels would benefit from closer surveillance. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.
    No preview · Article · Mar 2015 · Journal of Obstetrics and Gynaecology Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of this disease. In this communication, we present the clinical, biochemical and molecular profile of seventeen GA I patients from 15 unrelated families from India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln), c.401A>G (p.Asp134Gly), c.662T>C (p.Leu221Pro), c.881G>C (p.Arg294Pro), c.1173dupG (p.Asn392Glufs*5), c.1238A>G (p.Tyr413Cys) and c.1241A>C (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in Indian patients with GA I. An early diagnosis and timely intervention can improve the underlying prognosis. Molecular confirmation is helpful in providing genetic counselling and prenatal diagnosis in subsequent pregnancy.
    Full-text · Article · Mar 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Valproate is a commonly used anticonvulsant drug. Uridine 5΄-diphospho (UDP)-glucuronosyltransferase (UGT) contributes to around 50% of valproate metabolism and its polymorphisms may be important for explaining the considerable variation in valproate levels in patients with epilepsy. Aim: This study was aimed to analyze the genetic polymorphisms of UGT1A6 in Indian children with epilepsy and their potential influence on the pharmacokinetics of valproate. Setting and Design: This cross-sectional study was carried out in the Department of Pediatrics, All India Institutes of Medical Sciences (AIIMS), New Delhi, between March 2011 and July 2012. Materials and Methods: Children aged 3-12 years diagnosed with epilepsy on valproate monotherapy for at least 1 month were enrolled. They underwent a detailed clinical examination. The UGT1A6 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Random samples were checked by genetic sequencing. The steady-state plasma concentrations of valproate were measured by High Performance Liquid Chromatography (HPLC) and associated with UGT1A6 polymorphisms. Results: A total of 80 children were studied. The prevalence of UGT1A6 T19G was as follows: TT (45%), TG (38.8%), and GG (16.3%); that of UGT1A6 A541G was: AA (48.8%), AG (38.8%), and GG (12.5%); and that of UGT1A6 A552C was: AA (43.8%), AC (40%), and CC (16.3%). The association between valproate doses or standardized serum valproate concentration and the various UGT1A6 genotypes could not be studied reliably in this small study population. Conclusions: The frequencies of UGT1A6 geneotypes and alleles were reported in the study population.
    No preview · Article · Mar 2015 · Neurology India
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 1 Gaucher disease is an inherited lysosomal enzyme deficiency with variable age of symptom onset. Common presenting signs include thrombocytopenia, anemia, hepatosplenomegaly, bone abnormalities and, additionally in children, growth failure. Fifty-seven patients aged 3-62 years at the baseline of two phase III trials for velaglucerase alfa treatment were enrolled in the single extension study. In the extension, they received every-other-week velaglucerase alfa intravenous infusions for 1.2-4.8 years at 60 U/kg, although 10 patients experienced dose reduction. No patient experienced a drug-related serious adverse event or withdrew due to an adverse event. One patient died following a convulsion that was reported as unrelated to the study drug. Only one patient tested positive for anti-velaglucerase alfa antibodies. Combining the experience of the initial phase III trials and the extension study, significant improvements were observed in the first 24 months from baseline in hematology variables, organ volumes, plasma biomarkers and, in adults, the lumbar spine bone mineral density Z-score. Improvements were maintained over longer-term treatment. Velaglucerase alfa had a good long-term safety and tolerability profile and patients continued to respond clinically, which is consistent with the results of the extension study to the phase I/II trial of velaglucerase alfa. EudraCT number 2008-001965-27; identifier NCT00635427. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Mar 2015 · American Journal of Hematology
  • [Show abstract] [Hide abstract]
    ABSTRACT: To the Editor: Acrodermatitis enteropathica (AE) is a rare disorder of zinc metabolism [1]. Deficiency of essential amino acids and fatty acids may also induce acrodermatitis enteropathica like lesions. The proposed name for such lesions is acrodermatitis acidemia/acrodermatitis dysmetabolica [2]. We report two rare cases of organic-acidemias who developed these lesions.Case 1:A 35-d-old-boy, born to a non-consanguinous-couple, presented with refractory seizures, poor-feeding and lethargy since day-5-of-life. Neurological evaluation showed microcephaly, lethargy and central hypotonia. Magnetic Resonance Imaging (MRI) of the brain showed bilateral diffusely swollen, hyperintense cerebral white matter with T2-weighted hyperintensities in dorsal pons, cerebellar peduncles, cerebellar white matter, globus pallidus and posterior limb of internal capsule. The blood spot tandem mass spectroscopy (TMS) showed highly elevated leucine/ isoleucine and valine levels with low alanine levels which c ...
    No preview · Article · Feb 2015 · The Indian Journal of Pediatrics

  • No preview · Conference Paper · Feb 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis, requiring either invasive liver biopsy-enzyme assay or potentially hazardous fructose challenge test or expensive molecular genetic analysis. Therefore, worldwide there has been a trend towards finding "common mutations" in distinct ethnic groups to simplify the process of diagnosis. The nonspecific presentation of the disease often leads to diagnostic confusion with other metabolic liver disorders such as glycogenoses, galactosemia, and tyrosinemia. This leads to much delay in diagnosis with consequent harm to the patient.We report mutations in the ALDOB gene, from eleven Indian patients, seven of whom belong to the Agarwal community. Six patients from the Agarwal community and two non-Agarwal patients harbored one novel mutation, c.324+1G>A (five homozygous and one heterozygous), in the ALDOB gene. Haplotyping performed in families confirmed a founder effect. The community has been known to harbor founder mutations in other genes such as the MLC1, PANK2, and CAPN3 genes, thus providing another evidence for a founder effect in the community in case of HFI. This may pave the path for a simpler and quicker test at least for this community in India. In addition to the founder mutation, we report four other novel mutations, c.112+1delG, c.380-1G>A, c.677G>A, and c.689delA, and a previously reported mutation, c.1013C>T, in the cohort from India.
    Full-text · Article · Jan 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by cutaneous and ocular photosensitivity and an increased risk of developing cutaneous neoplasms. Progressive neurological abnormalities develop in a quarter of XP patients. To study the clinical profile and perform a mutation analysis in Indian patients with xeroderma pigmentosum. Ten families with 13 patients with XP were referred to our clinic over 2 years. The genes XPA, XPB and XPC were sequentially analyzed till a pathogenic mutation was identified. Homozygous mutations in the XPA gene were seen in patients with moderate to severe mental retardation (6/10 families) but not in those without neurological features. Two unrelated families with a common family name and belonging to the same community from Maharashtra were found to have an identical mutation in the XPA gene, namely c.335_338delTTATinsCATAAGAAA (p.F112SfsX2). Testing of the XPC gene in two families with four affected children led to the identification of the novel mutations c.1243C>T or p.R415X and c.1677C>A or p.Y559X. In two families, mutations could not be identified in XPA, XPB and XPC genes. The sample size is small. Indian patients who have neurological abnormalities associated with XP should be screened for mutations in the XPA gene.
    No preview · Article · Jan 2015 · Indian Journal of Dermatology Venereology and Leprology
  • Seema Kapoor · Sangeeta Gupta · Madhulika Kabra
    [Show abstract] [Hide abstract]
    ABSTRACT: Pediatricians are the first contact of a child with genetic disorders such as Down Syndrome. After diagnosis, parents often express and wish that if it was possible to detect it during pregnancy and could it be avoided in the future pregnancy. This makes it essential that pediatricians should have some idea about the basic screening methods and strategy used during pregnancy.
    No preview · Article · Dec 2014 · Indian pediatrics

  • No preview · Article · Oct 2014 · Genetics in medicine: official journal of the American College of Medical Genetics

Publication Stats

2k Citations
600.88 Total Impact Points


  • 2008-2015
    • AIIMS Bhopal All India Institute of Medical Sciences
      Bhopal, Madhya Pradesh, India
  • 1994-2015
    • All India Institute of Medical Sciences
      • Department of Paediatrics
      New Dilli, NCT, India
  • 2014
    • Lok Nayak Hospital
      New Dilli, NCT, India
  • 2013
    • Tulane University
      • Hayward Genetics Center
      New Orleans, Louisiana, United States
  • 2007
    • Council of Scientific and Industrial Research (CSIR), New Delhi
      New Dilli, NCT, India
  • 2006
    • Centre of Excellence in Molecular Biology
      Lāhaur, Punjab, Pakistan