Browsing by Author "Seema Kapoor"

Now showing 1 - 15 of 15

A clinical report of Chediak-Higashi syndrome in infancy with a novel genotype from the Indian subcontinent
(Blackwell Publishing Ltd, 2016) Ankur Singh; Melanie M. Bryan; Joseph C. Roney; Andrew R. Cullinane; William A. Gahl; Nita Khurana; Seema Kapoor
Chediak-Higashi syndrome (CHS; OMIM no. 214500) is an inherited multisystem disorder presenting with hypopigmentation and a propensity to infections due to immunological dysfunction. CHS generally presents in infancy with a fatal outcome, but less severe cases can present in adulthood. Treatment with bone marrow transplantation can be life-saving, so establishing a correct diagnosis is critical. The presence of large granules on examination of peripheral blood smears is suggestive of the diagnosis of CHS in most centers. However, sequencing of the lysosomal trafficking, LYST, gene confirms the diagnosis and can provide a prognosis regarding disease severity. In the case presented here, we performed molecular testing to identify the causative mutation and tabulated published mutation data from 2009 to 2014. We found a novel frameshift mutation in our case and concluded that frameshift and nonsense are the most common types of mutation in CHS, but this may be biased due to underdiagnosis of the milder and atypical forms of the disease. © 2016 International Society of Dermatology.
A novel CANT1 mutation in three Indian patients with Desbuquois dysplasia Kim type
(Elsevier Masson SAS, 2015) Ankur Singh; Ok-Hwa Kim; Aritoshi Iida; Woong-Yang Park; Shiro Ikegawa; Seema Kapoor
Desbuquois dysplasia (DBQD) is a rare skeletal dysplasia characterized by severe short stature, laxity, dislocation of multiple joints and developmental delay. DBQD is clinically heterogeneous. Distinct radiographic hand abnormalities such as the presence of extra-ossification distal to the second metacarpal or normal hand has led to its classification into types 1 and 2. Furthermore, the third type of DBQD, Kim type has been reported which is characterized by short metacarpals and elongated phalanges. However, DBQD Kim type has been exclusively reported in Japanese and Korean and its clinical characteristics remain to be delineated. Mutations in the calcium-activated nucleotidase 1 (. CANT1) gene have been reported in all three types of DBQD. Previously reported patients with DBQD Kim type had a common mutation c.676G>A (p.Val226Met), which had a common founder between Japanese and Korean. Here, we report 3 Indian patients with DBQD, Kim type from 2 families which were unrelated to each other. We identified a novel mutation of CANT1, c.467C>T (p.Ser156Phe), in all the patients in the homozygous form. Our results show that DBQD Kim type is not exclusive to East Asians and also report a novel mutation from the Indian subcontinent. © 2014 Elsevier Masson SAS.
Anastrozole-mediated modulation of mitochondrial activity by inhibition of mitochondrial permeability transition pore opening: an initial perspective
(Taylor and Francis Ltd., 2023) Somesh Kumar; Neha Choudhary; Mohammed Faruq; Arun Kumar; Ravindra K. Saran; Prem Kumar Indercanti; Vikram Singh; Haseena Sait; Sunita Jaitley; Martin Valis; Kamil Kuca; Sunil K. Polipalli; Manoj Kumar; Tejveer Singh; Prashanth Suravajhala; Rohit Sharma; Seema Kapoor
The mitochondrial permeability transition pore (mtPTP) plays a vital role in altering the structure and function of mitochondria. Cyclophilin D (CypD) is a mitochondrial protein that regulates mtPTP function and a known drug target for therapeutic studies involving mitochondria. While the effect of aromatase inhibition on the mtPTP has been studied previously, the effect of anastrozole on the mtPTP has not been completely elucidated. The role of anastrozole in modulating the mtPTP was evaluated by docking, molecular dynamics and network-guided studies using human CypD data. The peripheral blood mononuclear cells (PBMCs) of patients with mitochondrial disorders and healthy controls were treated with anastrozole and evaluated for mitochondrial permeability transition pore (mtPTP) function and apoptosis using a flow cytometer. Spectrophotometry was employed for estimating total ATP levels. The anastrozole–CypD complex is more stable than cyclosporin A (CsA)–CypD. Anastrozole performed better than cyclosporine in inhibiting mtPTP. Additional effects included inducing mitochondrial membrane depolarization and a reduction in mitochondrial swelling and superoxide generation, intrinsic caspase-3 activity and cellular apoptosis, along with an increase in ATP levels. Anastrozole may serve as a potential therapeutic agent for mitochondrial disorders and ameliorate the clinical phenotype by regulating the activity of mtPTP. However, further studies are required to substantiate our preliminary findings. Communicated by Ramaswamy H. Sarma. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Cleidocranial Dysplasia with Normal Clavicles: A Report of a Novel Genotype and a Review of Seven Previous Cases
(S. Karger AG, 2015) Ankur Singh; Mridula Goswami; Gaurav Pradhan; Min-Su Han; Je-Yong Choi; Seema Kapoor
We report an unusual combination of features comprising delayed tooth eruption and closure of the anterior fontanel as the sole presenting features in a child with cleidocranial dysplasia (CCD). Radiological survey revealed the presence of wormian bones in the skull, pseudoepiphysis at the base of the bilateral second metacarpal, and midline ossification defects at pubic symphysis in the presence of essentially normal clavicles. DNA sequencing of the RUNX2 gene detected a novel nonsense mutation in exon1 (c.166C>T; p.Q56X) in its glutamine-alanine (Q/A) repeat domain. The genotypes of all published cases of CCD with normal clavicles were reviewed. Additional dental and otolaryngological features were enlisted. Three cases with a milder dental phenotype and normal clavicles were associated with a mutation in the Q/A domain. Collectively, we found a novel CCD-causing nonsense mutation p.Q56X in the Q/A domain of the RUNX2 gene. © 2015 S. Karger AG, Basel.
Clinical and metabolic profile of glutaric aciduria type 1 from North India: Tertiary centre experience
(Journal of Clinical and Diagnostic Research, 2017) Ankur Singh; Rajniti Prasad; Seema Kapoor; Om Prakash Mishra
Introduction: Glutaric aciduria type 1 is caused by deficiency of glutaryl-CoA dehydogenase leading to accumulation of glutarylcarnitine in blood and excretion of glutaric acid, 3-hyroxyglutaric acid and glutaconic acid in urine. It can be diagnosed through high risk screening in symptomatic cases. Aim: To know the clinical, biochemical, neuroimaging and outcome profile of Glutaric aciduria type 1 patient diagnosed during testing by Tandem Mass Spectrometry (TMS) and Gas Chromatography and Mass Spectrometry (GCMS). Materials and Methods: It was retrospective record analysis of patients diagnosed with Glutaric aciduria type 1. 2000 patients were screened for various indications like (developmental delay/regression, unexplained seizures, encephalopathy, dystonia, chorea, large head, unexplained sibling death). Screening strategy involved estimation of lactate, ammonia, TMS and GCMS. Neuroimaging was done where it was required. This study was conducted over a period of three years (Jan 2014 to Dec 2016). Results: Study group comprised of 10 males and 3 females. Median age (interquartile range) of presentation in study group was 11 months (10-22.5). Pretesting diagnosis was suspected as inborn error of metabolism in each case based on clinical presentation. Seizure and dystonia were important clinical presentation. Frontotemporal atrophy was important neuroimaging finding. Macrocephaly was present in two of thirteen cases. Glutarylcarnitine level was normal in 5 of 11 patients, suggesting poor sensitivity of TMS in diagnosed cases. There was wide variation in excretion of urinary metabolite from cases to cases, highlighting genetic heterogenousity. Conclusion: Seizures and dystonia were important clinical presentations. Presence of bilateral frontotemporal atrophy in clinical testing was an important clue to diagnosis. Presence of macrocephaly (important sign of disease) was present in only two cases. There was only one death in follow up. © 2017, Journal of Clinical and Diagnostic Research. All rights reserved.
Clinical, biochemical and outcome profile of biotinidase deficient patients from tertiary centre in Northern India
(Journal of Clinical and Diagnostic Research, 2015) Ankur Singh; Avinash Lomash; Sanjeev Pandey; Seema Kapoor
Introduction: Biotinidase deficiency is an inherited metabolic disorder with estimated birth incidence of 1 in 61,000 for profound and partial deficiency. Estimated incidence of profound and partial biotinidase deficiency is 1 in 1, 37,000 and 1 in 1, 10,000 respectively. The carrier frequency in general population is 1 in 120. We attempt to study clinical, biochemical and outcome from 10 Biotinidase deficient patients. Materials and Methods: A retrospective case record study was conducted to record Clinical, biochemical and outcome profile from genetic records. Biotinidase level was measured using spectrophotometric method. Results: Study group comprised of 8 males and 2 females with median age of presentation 6 (2-45.75) months. Median (interquartile range) Biotinidase level in study group 0.3 (0.08—1.5) nmol/ml/min. Study group was further divided in to early onset group (< 12 months, n-6) and late onset group (> 12 months, n-4). Seizure, alopecia and hearing loss were predominant phenotypes in study group. The other rare presentations were: hypotonia, ataxia, skin rash, seborrhoea. The most common seizure type was focal seizure. Control of seizure activity was important immediate outcome measured in study group. Median duration (interquartile range) of seizure control in early onset group was 3 (2-4)days against 13.5 (12.25-14.75) days in late onset group. Conclusion: This study highlights the need of early diagnosis for favourable outcome for a potentially treatable inherited metabolic disorder. © 2015, Journal of Clinical and Diagnostic Research. All rights reserved.
Estimation of Biomarkers Chitotriosidase and CCL18/PARC in Gaucher Patients: Indian Experience
(Springer India, 2015) Sanjeev Pandey; Ankur Singh; A.P. Dubey; T.K. Mishra; Seema Kapoor
Gaucher disease (GD) is caused by a deficient activity of the enzyme glucocerebrosidase. Recent review from India suggests GD to constitute 14.6 % of all LSD’s. Chitotriosidase has been used for assessing the disease burden and response to enzyme replacement therapy in most of developed countries and in few centers in our country. This biomarker is of limited utility in cases who have inherited mutated chitotriosidase gene, leading to normal to low level of biomarker and thus not correlating with disease burden. CCL18/PARC is a relatively new biomarker which had not been estimated in gaucher patients in India. This study tends to measure quantity of CCL18/PARC in Gaucher patients at various time intervals. The study was conducted at a tertiary care center in North India. Fourteen patients with deficient glucocerebrosidase activity were enrolled as cases. Clinical and biochemical parameters were recorded in predefined proforma. Enzyme glucocerebrosidasae was estimated as per protocol. The level of enzyme Chitotriosidase, CCL18/PARC was performed by using a commercially available ELISA kit. We evaluated chitotriosidase and CLL18/PARC levels in plasma of 10 type 1 GD patients, two with type 2 GD and two with type 3 GD. The median level of chitotriosidase were 259.3 (182–452.1) ng/ml at the time of recruitment {base line}, 332 (216.3–422.5) ng/ml, {1 year after base line}, 331.35 (222.2–434.6) ng/ml {2 years after base line}. The median levels of CCL18/PARC were 484.1 (334.2–592.5) ng/ml at the time of recruitment (baseline), 448.2 (399.2–702) ng/ml, {1 year after base line}, 431.75(362.1–689) ng/ml {2 years after base line}.We conclude that plasma CCL18 levels can serve as a dependable biomarker in patients with Gaucher disease and of significant utility in patients deficient in chitotriosidase enzyme. © 2014, Association of Clinical Biochemists of India.
Expanding the genetic and phenotypic spectrum of popliteal pterygium disorders
(Wiley-Liss Inc., 2015) Elizabeth J. Leslie; James O'Sullivan; Michael L. Cunningham; Ankur Singh; Steven L. Goudy; Faroug Ababneh; Lamia Alsubaie; Gaik-Siew Ch'ng; Ingrid M. B. H. van der Laar; A. Jeannette M. Hoogeboom; Martine Dunnwald; Seema Kapoor; Pawina Jiramongkolchai; Jennifer Standley; J. Robert Manak; Jeffrey C. Murray; Michael J. Dixon
The popliteal pterygia syndromes are a distinct subset of the hundreds of Mendelian orofacial clefting syndromes. Popliteal pterygia syndromes have considerable variability in severity and in the associated phenotypic features but are all characterized by cutaneous webbing across one or more major joints, cleft lip and/or palate, syndactyly, and genital malformations. Heterozygous mutations in IRF6 cause popliteal pterygium syndrome (PPS) while homozygous mutations in RIPK4 or CHUK (IKKA) cause the more severe Bartsocas-Papas syndrome (BPS) and Cocoon syndrome, respectively. In this study, we report mutations in six pedigrees with children affected with PPS or BPS. Using a combination of Sanger and exome sequencing, we report the first case of an autosomal recessive popliteal pterygium syndrome caused by homozygous mutation of IRF6 and the first case of uniparental disomy of chromosome 21 leading to a recessive disorder. We also demonstrate that mutations in RIPK4 can cause features with a range of severity along the PPS-BPS spectrum and that mutations in IKKA can cause a range of features along the BPS-Cocoon spectrum. Our findings have clinical implications for genetic counseling of families with pterygia syndromes and further implicate IRF6, RIPK4, and CHUK (IKKA) in potentially interconnected pathways governing epidermal and craniofacial development. © 2015 Wiley Periodicals, Inc.
Expanding the phenome and variome of skeletal dysplasia
(Nature Publishing Group, 2018) Sateesh Maddirevula; Saud Alsahli; Lamees Alhabeeb; Nisha Patel; Fatema Alzahrani; Hanan E Shamseldin; Shams Anazi; Nour Ewida; Hessa S Alsaif; Jawahir Y Mohamed; Anas M Alazami; Niema Ibrahim; Firdous Abdulwahab; Mais Hashem; Mohamed Abouelhoda; Dorota Monies; Nada Al Tassan; Muneera Alshammari; Afaf Alsagheir; Mohammed Zain Seidahmed; Samira Sogati; Mona S Aglan; Muddathir H Hamad; Mustafa A Salih; Ahlam A Hamed; Nadia Alhashmi; Amira Nabil; Fatima Alfadli; Ghada M H Abdel-Salam; Hisham Alkuraya; Winnie Ong Peitee; W.T. Keng; Abdullah Qasem; Aziza M Mushiba; Maha S Zaki; Mahmoud R Fassad; Majid Alfadhel; Saji Alexander; Yasser Sabr; Samia Temtamy; Alka V Ekbote; Samira Ismail; Gamal Ahmed Hosny; Ghada A Otaify; Khalda Amr; Saeed Al Tala; Arif O Khan; Tamer Rizk; Aida Alaqeel; Abdulmonem Alsiddiky; Ankur Singh; Seema Kapoor; Amal Alhashem; Eissa Faqeih; Ranad Shaheen; Fowzan S Alkuraya
Purpose: To describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized. Methods: Detailed phenotyping and next-generation sequencing (panel and exome). Results: Our analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello–Carey syndrome–like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average. Conclusion: By expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions. © 2018, American College of Medical Genetics and Genomics.
Genetic Analysis of Jervel and Lange Nielsen Syndrome with a Novel Mutation in KCNQ1 Gene
(Springer India, 2016) Ankur Singh; Rajniti Prasad; Royana Singh; Seema Kapoor; Zahurul A. Bhuiyan; Om Prakash Mishra
[No abstract available]
I Cell Disease (Mucolipidosis II Alpha/Beta): From Screening to Molecular Diagnosis
(Springer India, 2017) Ankur Singh; Rajniti Prasad; Aditya Kumar Gupta; Anil Sharma; Sandra Alves; Maria Francisca Coutinho; Seema Kapoor; Om Prakash Mishra
Mucopolysaccharidosis (MPS) and Mucolipidosis (ML) share common phenotypes (coarse facial features, organomegaly, dysostosis multiplex) despite having different molecular basis. Thus, they pose great diagnostic challenge to treating clinicians. Differentiating between the two conditions requires a battery of tests from screening to molecular diagnosis. Besides discussing differential diagnosis of MPS like features with negative urinary Glycosaminoglycans (GAG), the authors also discuss the utility of p-nitrocatechol sulphate based chemical test as an important screening tool, besides establishing molecular basis in index case. © 2016, Dr. K C Chaudhuri Foundation.
Identification of a novel MKS locus defined by TMEM107 mutation
(Oxford University Press, 2015) Ranad Shaheen; Agaadir Almoisheer; Eissa Faqeih; Zainab Babay; Dorota Monies; Nada Tassan; Mohamed Abouelhoda; Wesam Kurdi; Elham Al Mardawi; Mohamed M.I. Khalil; Mohammed Zain Seidahmed; Maha Alnemer; Nada Alsahan; Samira Sogaty; Amal Alhashem; Ankur Singh; Manisha Goyal; Seema Kapoor; Rana Alomar; Niema Ibrahim; Fowzan S. Alkuraya
Meckel-Gruber syndrome (MKS) is a perinatally lethal disorder characterized by the triad of occipital encephalocele, polydactyly and polycystic kidneys. Typical of other disorders related to defective primary cilium (ciliopathies), MKS is genetically heterogeneous with mutations in a dozen genes to date known to cause the disease. In an ongoing effort to characterize MKS clinically and genetically, we implemented a gene panel and next-generation sequencing approach to identify the causal mutation in 25 MKS families. Of the three families that did not harbor an identifiable causal mutation by this approach, two mapped to a novel disease locus in which whole-exome sequencing revealed the likely causal mutation as a homozygous splicing variant in TMEM107, which we confirm leads to aberrant splicing and nonsense-mediated decay. TMEM107 had been independently identified in two mouse models as a cilia-related protein and mutant mice display typical ciliopathy phenotypes. Our analysis of patient fibroblasts shows marked ciliogenesis defect with an accompanying perturbation of sonic hedgehog signaling, highly concordant with the cellular phenotype in Tmem107 mutants. This study shows that known MKS loci account for the overwhelming majority of MKS cases but additional loci exist including MKS13 caused by TMEM107 mutation. © The Author 2015. Published by Oxford University Press. All rights reserved.
Pendred syndrome in a newborn with neck swelling: A case report
(Oxford University Press, 2016) Mohemmed Ajij; Shambhavi; Bijoy Patra; Ankur Singh; Seema Kapoor
Background: Pendred syndrome is a rare autosomal recessive condition, characterized by functional impairment of thyroid gland and sensorineural hearing loss. The syndrome presents in patients with homozygous or compound heterozygous mutation. The presentation in the form of neck mass in a newborn is rare. Case characteristics: A 1 month old baby presented to us with neck mass, which was found to be an enlarged thyroid gland. Thyroid function tests were consistent with hypothyroidism. Further evaluation revealed moderate sensorineural hearing loss; genetic analysis showed that baby was homozygous for the known mutations causing the disease. Intervention: Thyroid hormone replacement and hearing habilitation were done. Follow up showed regression of the neck mass and normalization of thyroid function tests. Genetic counseling of the family was done. Message: Identification of the exact cause of congenital hypothyroidism can prevent grave consequences later on for the patient as well as for the family. © The Author [2016]. Published by Oxford University Press. All rights reserved.
Spectrum of disproportionate short stature at a tertiary-care center in Northern India
(Springer India, 2017) Ankur Singh; Gaurav Pradhan; Rajniti Prasad; Om Prakash Mishra; Seema Kapoor
Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from genetic clinic of Lok Nayak Hospital, Delhi were assessed in this study. Achondroplasia was the commonest (n=9) skeletal dysplasia; conclusive diagnosis was not possible in six children. Molecular confirmation of clinicoradiological phenotype was done in 18 of 40 cases. Genetic study of all achondroplasia cases revealed c. 1138 G>A, p. Gly380Arg mutation in hot spot. © 2017, Indian Academy of Pediatrics.
Transmission of Barber-Say syndrome from a mosaic father to his child in an Indian family
(Lippincott Williams and Wilkins, 2016) Ankur Singh; Denny Schanze; Neha Agarwal; Rajniti Prasad; Om Prakash Mishra; Royana Singh; Seema Kapoor; Martin Zenker
[No abstract available]