WITHDRAWN: Mutational analysis of the F8 gene and phenotypic characterization of Hemophilia A.

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Total Reflection X-ray Fluorescence Analysis of Plasma Elements in Autistic Children from India.

Trace elements are essential for the human body's various physiological processes but if they are present in higher concentration, these elements turn to be toxic and cause adverse effect on physiological processes. Similarly, deficiency of these essential elements also affects physiological processes and leads to abnormal metabolic activities. There is a lot of interest in recent years to know the mystery behind the involvement of trace elements in the metabolic activities of autistic children suspecting that it may be a risk factor in the aetiology of autism. The present study aims to analyse the plasma trace elements in autistic children using the total reflection X-ray fluorescence (TXRF) technique. Plasma samples from 70 autistic children (mean age: 11.5 ± 3.1) were analysed with 70 age- and sex-matched healthy children as controls (mean age: 12 ± 2.5). TXRF analysis revealed the higher concentration of copper (1227.8 ± 17.8), chromium (7.1 ± 2.5), bromine (2695.1 ± 24) and arsenic (126.3 ± 10) and lower concentration of potassium (440.1 ± 25), iron (1039.6 ± 28), zinc (635.7 ± 21), selenium (52.3 ± 8.5), rubidium (1528.9 ± 28) and molybdenum (162,800.8 ± 14) elements in the plasma of autistic children in comparison to healthy controls. Findings of the first study from India suggest these altered concentrations in elements in autistic children over normal healthy children affect the physiological processes and metabolism. Further studies are needed to clarify the association between the altered element concentration and physiology of autism in the North Karnataka population in India.

Clinical profile of hemophilia B patients from Karnataka.

Background: The most prevalent severe inherited hemorrhagic condition is hemophilia, which means "love of blood." Hemophilia A and B are caused by a lack or malfunction of the factor VIII and factor IX proteins. Objective: The present study is to determine the prevalence and clinical profile of hereditary coagulation disorder, particularly hemophilia B, in Karnataka. Methods: The study comprised 150 HB patients with a mean age of 25, nmale = 148 and nfemale = 2. The samples were collected from hemophilia societies across Karnataka. The detailed history of HB patients was recorded in a predesigned Performa regarding family history, age, time of first bleed, site of the bleed, and bleeding history. Result: In our study cohort, the majority of the 58 (38.7%) cases belong to 21-30 years of age. The mean age of onset was 2.0 ± 1.0 years in severe, 7.5 ± 2.8 0 years in moderate, and 10.0 ± 3.5 years in mild HB patients. Out of 150 HB cases, 102 (68%) cases were diagnosed as severe, 30 (20%) as moderate, and 18 (12%) as mild. Mean factor IX levels were 0.6 ± 0.2, 2.5 ± 1.3, and 8.0 ± 2.6 in the severe, moderate, and mild group, respectively. A family history of bleeding was observed in 97 [64.7%] HB patients. Forty-seven (32.3%) HB patients had a history of consanguinity. The most common initial site of bleed was in joints in 86 [57.3%]. Conclusion: The present study is one of the fewer studies from Karnataka studying the demographic and clinicopathological features of hemophilia B. Early diagnosis can be only helpful with knowledge of spectral presentation of hemophilia B in a local population.

Mutation analysis and characterisation of F9 gene in haemophilia- B population of India.

BACKGROUND: Hemophilia B (HB) is an X-linked bleeding disorder resulting from coagulation factor IX defects. Over 3,000 pathogenic, HB-associated mutations in the F9 gene have been identified. We aimed to investigate the role of F9 variants in 150 HB patients using sequencing technology. METHODS: F9 gene sequences were amplified from peripheral blood-derived DNA and sequenced on an Applied Biosystems (ABI) 3500 Sanger sequencing platform. Functional and structural predictions of mutant FIX were analyzed. RESULTS: Among 150 HB patients, 102 (68%), 30 (20%), and 18 (12%) suffered from severe, moderate, and mild HB, respectively. Genetic analysis identified 16 mutations, including 3 novel mutations. Nine mutations (7 missense and 2 stop-gain) were found to be pathogenic. Only 3 mutations (c.127C＞T, c.470G＞A, and c.1070G＞A) were associated with different severities. While 2 mutations were associated with mild HB cases (c.304C＞T and c.580A＞G), 2 (c.195G＞A and c.1385A＞G) and 3 mutations (c.223C＞T, c.1187G＞A, and c.1232G＞A) resulted in moderate and severe disease, respectively. Additionally, 1 mutation each was associated with mild-moderate (c.*1110A＞G) and mild-severe HB disease (c.197A＞T), 4 mutations were associated with moderate-severe HB cases (c.314A＞G, c.198A＞T, c.676C＞T, and c.1094C＞A). FIX concentrations were lower in the mutated group (5.5±2.5% vs. 8.0±2.5%). Novel p.E66D and p.S365 mutations were predicted to be pathogenic based on changes in FIX structure and function. CONCLUSION: Novel single nucleotide polymorphisms (SNPs) largely contributed to the pathogenesis of HB. Our study strongly suggests that population-based genetic screening will be particularly helpful to identify risk prediction and carrier detection tools for Indian HB patients.

Prevalence and distribution of high risk human papillomavirus (HPV) Types 16 and 18 in Carcinoma of cervix, saliva of patients with oral squamous cell carcinoma and in the general population in Karnataka, India.

BACKGROUND: In view of conducting HPV vaccination in India it is most important to understand the prevalence of HPV genotypes in this population, not only in squamous cell carcinoma of cervix and oral cavity but also in the general population. In this study we explored the prevalence and distribution of high-risk HPV types 16 and 18 in carcinoma of cervix, saliva of patients with oral squamous cell carcinoma and in general population in Karnataka. METHODS: Cervical cancer specimens after punch biopsy (n=60) were obtained from women attending Karnataka Institute of Medical Sciences and Karnataka Cancer Therapy and Research Institute, Hubli (KCTRI). Saliva rinse of (n=34) OSCC patients from KCTRI and (n=396) normal individuals from different regions of North Karnataka, were collected and PCR based high-risk HPV genotyping was carried out. RESULTS: Using consensus PCR primers it was observed that 96.7% patients were infected with HPV irrespective of specific type in cervical cancer. Among them, HPV 16 was observed in 89.7%, HPV 18 in 86.2% and both HPV 16 and 18 in 79.3% patients. In OSCC, 70.6% were positive for HPV, among which HPV 16 prevalence was observed in 45.8%, HPV 18 in 54.2%, and HPV 16 and 18 multiple infection in 4.18%. In general population, HPV prevalence was observed in 84.4%. Among them, HPV 16 was observed in 2.75% and HPV 18 in 22.0% patients. In general population, multiple infection with HPV 16 and 18 was not observed but 75.3% were found to be infected by HPV genotypes other than HPV 16 and 18. CONCLUSIONS: Our study reveals that multiple infection of HPV 16 and 18 is quite high in cervical cancer and in case of OSCC, it was in conformity with the other studies. In general population HPV 18 prevalence was observed to be high. With this, we can conclude that both HPV 16 and 18 vaccinations will reduce the burden of cervical cancer and OSCC in Karnataka.