Variation in Exon 29 of the NOS1 Gene Does Not Contribute to Parkinson's Disease in the North Karnataka Population.

INTRODUCTION: Nitric oxide (NO) overproduction has been found to have neurotoxic effects on the brain. Moreover, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced, the suppression of the NO-synthesizing enzymes, such as neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS), has neuroprotective benefits in Parkinson's disease (PD). These findings imply that NOS may have a role in regulating the nigral dopaminergic neurons' tolerance to environmental stressors in PD. OBJECTIVE: In the present study, we investigated variations in the NOS1 gene that may raise the likelihood of PD. METHODS: PD patients who visited the neurology departments of several medical colleges and hospitals in North Karnataka, India, between 2009 and 2011 were included in the study. The detailed clinic pathological details were obtained from 100 PD patients. Genomic DNA was isolated using the kit method followed by the evaluation of the quality and quantity of isolated gDNA. Polymerase chain reaction (PCR) amplification of exon 29 was performed, and sequencing was performed using the Applied Biosystems ABI 3500 Sanger sequencing platform. RESULTS: The present study is comprised of 100 PD patients, which includes 65 males and 35 females. There were 64 sporadic, 34 idiopathic, and two familial PD cases. The majority (67.1%) of PD cases were from metropolitan areas. Community-based segregation showed that the maximum cases were from Hindu Lingayat. A proportion (90.8%) of the patients had tremors, 32.7% of them displayed slowness in their daily tasks, and 8.1% of them had dyskinesia. Molecular analysis showed two untranslated region (UTR) variations g.151787 del T (rs1434015950) and g.151745 C>T (rs2682826) in our study group. CONCLUSION: The absence of mutations in the targeted NOS1 gene in the PD patients from North Karnataka shows the involvement of other genes in the molecular pathophysiology. Thus, it is crucial to screen other possible genes using cutting-edge technology to obtain a clear picture of the genetics of PD.

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.

Analysis of Genetic Variations in Connexin 26 ( GJB2 ) Gene among Nonsyndromic Hearing Impairment: Familial Study.

Objective The goal of this research was to investigate the gap junction beta 2 ( GJB2 ) gene mutations associated with nonsyndromic hearing loss individuals in North Karnataka, India. Materials and Methods For this study, patients with sensorineural genetic hearing abnormalities and a family history of deafness were included. A total of 35 patients from 20 families have been included in the study. The patient's DNA was isolated from peripheral blood samples. The GJB2 gene coding region was analyzed through Sanger sequencing. Results There is no changes in the first exon of the GJB2 gene. Nine different variants were recorded in second exon of the targeted gene. W24X and W77X are two nonsense mutations and three polymorphisms viz. R127H, V153I, and I33T were reported along with four 3'-UTR variants. A total (9/20) of 45% of families have been identified with mutations in the targeted gene. Conclusion GJB2 mutations were identified in 19 deaf-mute patients (19/35), and 13 patients were homozygous for the mutations identified in our study cohort. In our study, W24X mutation was found to be the pathogenic with a high percentage, prompting further evaluation of the other genes, along with the study of additional genetic or external causes in the families, which is essential.

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.