Divya Gupta

Association of TNF-α -308G>A and TNF-β +252A>G genes polymorphisms with primary immune thrombocytopenia: a North Indian study.

Primary immune thrombocytopenia (ITP) is manifested by platelet autoantibodies that are not only responsible for platelet destruction by phagocytosis but also inhibit their production. Bleeding is the most common clinical manifestation of thrombocytopenia. ITP is a multifactorial disease in which both environmental and genetic factors have been implicated. It has been reported that several gene polymorphisms influence host susceptibility to ITP. This study was aimed to investigate the association of polymorphisms in tumor necrosis factor-alpha (TNF-&agr;) 308 G>A and TNF-&bgr; +252 A>G genes with primary ITP in Indian patients. Genotyping for the TNF-&agr; −308 G>A and TNF-&bgr; +252 A>G was performed in 80 ITP patients and 100 controls by polymerase chain reaction and restriction fragment length polymorphism. We found no significant difference in distribution of TNF-&agr; heterozygous variant genotype (GA) among patients and controls. Homozygous variant genotype (AA) was absent both in patients and controls. No statistical difference was observed in the distribution of heterozygous variant (AG) and homozygous variant (GG) genotypes of TNF-&bgr;, between patients and controls. Heterozygous (AG) genotype of TNF-&bgr; −308G>A was associated with persistent ITP. The study showed that heterozygous variant (AG) genotype of TNF-&bgr; was associated with persistent ITP, when compared with controls. We could not find any association of TNF-&agr; with susceptibility in developing ITP. Furthermore, no association was observed with respect to different categories of ITP. In addition, additive model showed two-fold increased susceptibility to ITP. We conclude that single nucleotide polymorphism in TNF-&bgr; +252 A>G gene may have impact on susceptibility to ITP.

Study of Polymorphisms in CX3CR1, PLEKHA1 and VEGF Genes as Risk Factors for Age-related Macular Degeneration in Indian Patients

BACKGROUND AND AIMSnAge-related macular degeneration (AMD) is an important cause of visual impairment in elderly persons. AMD is a multifactorial disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been found to be associated with AMD. This study aimed to investigate the association of polymorphisms in CX3CR1, PLEKHA1 and VEGF genes with AMD in Indian patients.nnnMETHODSnGenotyping for the CX3CR1 T280M (C>T) and V249I (G>A), PLEKHA1 A320T (G>A) &VEGFxa0+674 (C>T) andxa0+936 (C>T) was performed in 121 AMD patients and 100 controls by polymerase chain reaction, restriction fragment length polymorphism (PCR-RFLP) and sequencing method.nnnRESULTSnThe genotype analysis of VEGF gene polymorphisms (+674 andxa0+936) showed a significant association with AMD. Odds ratios for VEGF (+674) and VEGF (+936) were 2.37 and 2.50 with a p value 0.0029 and 0.0358 for the autosomal dominant model. CX3CR1 (T280M and V249I) and PLEKHA1 (A320T) polymorphisms were not found to be associated with AMD. Odds ratios for mutant alleles of T280M and V249I polymorphisms in CX3CR1 gene were 0.95 and 0.83, respectively, compared to the wild-type alleles. Odds ratio for the polymorphism in the PLEKHA1 gene was 0.63.nnnCONCLUSIONSnThe present study suggests that both polymorphisms in VEGF gene are risk factors for AMD in the Indian population. Detection of individuals at risk could lead to strategies for prevention, early diagnosis and management of AMD.

COL1A1 Mutation in an Indian Child with Caffey Disease

Caffey disease or infantile cortical hyperostosis is a rare skeletal disorder with both sporadic and familial occurrence. The autosomal dominant familial form has been found to be a collagenopathy. The case being reported is a 7- month-old Indian boy with Caffey disease who was found to have the R1014C heterozygous mutation in the COL1A1 gene. This is the first mutation report of an Indian case with Caffey disease.

Vascular endothelial growth factor gene polymorphisms and association with age related macular degeneration in Indian patients

Background Age-related macular degeneration (AMD) is an important cause of visual impairment in elderly people. AMD is a multifactorial disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been found to be associated with AMD. Aim This study was aimed to investigate the association of polymorphisms in VEGF genes with age related macular degeneration (AMD) in Indian patients. Method Genotyping for the VEGF − 1154 (G > A), − 2578 (C > A), + 405 (G > C) and − 460 (C > T) SNPs was performed in 100 AMD patients and 100 controls by polymerase chain reaction (PCR), restriction fragment length polymorphism (PCR-RFLP) and sequencing method. Results Out of the four SNPs, heterozygous genotypes of VEGF − 1154 G > A (OR = 2.58, p = 0.0035), + 460 C > T (OR = 2.90, p = 0.0046), and + 405 G > C (OR = 2.02, p = 0.02) have shown susceptible association with AMD. However, VEGF − 2578 C > A did not show any statistical significance. Further A-A-G-T haplotype comprising of three mutant alleles revealed risk association (OR = 12.7, p = 0.0030) with AMD. Conclusion The present study suggests significant genetic associations for VEGF − 1154 G > A, + 460 C > T, and + 405 G > C polymorphisms with AMD. Early detection of individuals with risk to these SNPs could lead to strategies for prevention, early diagnosis, and management of AMD.

Fibrodysplasia Ossificans Progressiva: Three Indian Patients with Mutation in the ACVR1 Gene

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by ectopic bone formation involving the connective tissues leading to severe skeletal manifestations. The genetic defect in this disorder has not been characterized in Indian patients till date. The authors report three cases of FOP along with the molecular defects identified in them. Exon 4 of the ACVR1 gene was amplified and analysed by sequencing. All three cases revealed common heterozygous mutation i.e., c.617(G>A). Identification of this mutation would lead to decrease in misdiagnosis and subsequent iatrogenic harm caused to these children by unnecessary surgical procedures. Also, mutation detection would provide an opportunity for prenatal diagnosis.

Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL-1Ra) gene polymorphisms in primary immune thrombocytopenia

Background Immune thrombocytopenia (ITP) is an immune-mediated disease caused by autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX. The etiology of ITP remains unclear. This study evaluated the association of polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP. Methods Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients and 100 controls by polymerase chain reaction restriction fragment length polymorphism and detection of variable number tandem repeats. Results Genotype differences in IL-1B-31 and IL-1Ra were significantly associated with ITP. Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52-fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence interval [CI]=1.04–2.22, P=0.034). The frequencies of both homozygous and heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069–5.09, P=0.033 and OR=2.044, 95% CI=1.068–39, P=0.034) among patients and were significantly associated with ITP susceptibility. Both homozygous and heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95% CI=1.17–17.05, P=0.0230 and OR=1.80, 95% CI=1.03–3.14, P=0.0494) among patients and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant association with severe ITP. However, IL-1B-511 was not associated with ITP. Conclusion IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk, and they could be associated with disease severity, which may contribute to the pathogenesis of ITP.

Molecular Characterization of Human Adenoviruses in Children Suffered From Acute Gastroenteritis By Partial Hexon Region

Viral gastroenteritis is an important cause of childhood morbidity and mortality, in developing countries [1]. Every year 2.5 million deaths are estimated to occur due to enteric infections, greatly impacting children younger than five years of age [2]. Human adenovirus (HAdV) creates a major risk in children, elderly people and immunocompromised persons [3]. It causes acute diarrhea at irregular intervals as well as in outbreaks [4]. HAdV can cause a broad range of human diseases such as acute respiratory tract infection (ARTI), pneumonia, bronchitis, conjunctivitis, hepatitis, ocular infection, hemorrhagic cystitis, gastroenteritis, GI and urinary tract infection (UTI). HAdV infectivity is transmitted by inhalation and direct contact with small droplet aerosols or the fecal-oral route [5]. HAdV discovered in 1953 and its prevalence is approximately 4-12% in acute gastroenteritis (AGI) and ARTI [6]. It belongs to the family Adenoviridae and genus Mastadenovirus and these are non-enveloped, icosahedral viruses. Adenoviruses have linear double-stranded DNA that generally range from 26 to 45 kb and Abstract

Unusual skin manifestations in a patient with menkes disease

Unusual Skin Manifestations in a Patient with Menkes Disease Divya Gupta, Raghavendra Rao, Katta M. Girisha, Joshi Stephen, and Shubha R. Phadke* Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India Department of Dermatology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, Udupi, Karnataka, India

Brothers with hypospadias, vertebral segmentation defects, and intellectual disability: new syndrome?

We report on two brothers (born to nonconsanguineous parents) with short stature, hypospadias, scoliosis, vertebral segmentation defects of “spondylocostal dysostosis” type, and intellectual disability. Results of cytogenetic and molecular genetic tests performed, including routine karyotype, MLPA (multiplex ligation‐dependent probe amplification) for common microdeletions and subtelomeric copy number variants, microarray‐CGH analysis, and sequencing of four Notch signaling pathway genes (DLL3, MESP2, LFNG, and HES7), were all normal. We present a comparison of the condition in the two boys with known syndromes and suggest that they may represent a hitherto unreported syndrome, most likely following autosomal recessive inheritance, though X‐linked inheritance is not excluded.