Nahid Khan - Academia.edu (original) (raw)

Papers by Nahid Khan

International Journal of Clinical and Experimental Physiology, 2021

Background and Aim: Polycystic ovary syndrome (PCOS) and thyroid disorders are commonest endocrin... more Background and Aim: Polycystic ovary syndrome (PCOS) and thyroid disorders are commonest endocrine disorders; both of these disorders have profound effect on reproductive function in women's. An increase in ovarian volume and cystic changes in ovaries have been reported in hypothyroidism. Recent studies reveal that PCOS might be associated with cardiovascular autonomic dysfunction and the thyroid hormone also influences the autonomic nervous system. So the aim of the study was to first, evaluate and compare autonomic function in PCOS as well as in PCOS with hypothyroidism, second, correlation between thyroid stimulating hormone (TSH) and autonomic function tests (AFT) in both the groups and third, study also provided further exploration in autonomic function in PCOS in presence of hypothyroidism. Methods: Total 43 newly diagnosed not on medications subjects were recruited, these subjects were divided into group A PCOS (n=33) and group B PCOS with hypothyroidism (n=10). Anthropometric measurements were taken from all the participants and autonomic function tests for assessing parasympathetic function (such as heart rate response to immediate standing and standing to lying ratio) and sympathetic function (such as blood pressure response to immediate standing and mental arithmetic stress test) were employed, then measurements was taken according to the respective scoring procedures. Results: In our studied population PCOS as well as PCOS with hypothyroidism showed autonomic dysfunction but no significant difference was found between them. No correlation and significance was found between TSH and AFT in both the groups. Conclusion: Our study concluded that the presence of hypothyroidism did not further affect autonomic function in PCOS and TSH was unrelated to AFT.

International Journal of Clinical and Experimental Physiology, 2015

Reports on autonomic dysfunction associated with obesity in adolescent population are limited and... more Reports on autonomic dysfunction associated with obesity in adolescent population are limited and also are conflicting. Therefore in the present study, we have evaluated the difference in autonomic function between the obese and nonobese adolescents. Sixty-five adolescent subjects aged between 17 and 19 years were selected from HAHC Hospital, Jamia Hamdard. Based on their body mass index, these subjects were divided into a nonobese group (n = 54) and obese group (n = 11). Autonomic function tests for assessing parasympathetic function (such as heart rate response to immediate standing and standing to lying ratio) and sympathetic function (such as blood pressure response to immediate standing and cold pressor test) were employed. There was no difference in sympathetic and parasympathetic function between the obese and nonobese adolescents. Therefore, the findings of the present study suggest that the autonomic dysfunction was not statistically significant in the studied adolescent population.

Indian Journal of Medical Research, 2015

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical pres... more Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.

Neuropediatrics, 2015

Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene (MT... more Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene (MT-ND5) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G > A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A > G mutation had episodic regression, progressive ataxia, optic atrophy, and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate, and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic-genetic testing and prognostication.

Mitochondrion, 2015

Complete mitochondrial DNA (mtDNA) analysis of 114 HCM patients along with 300 ethnically matched... more Complete mitochondrial DNA (mtDNA) analysis of 114 HCM patients along with 300 ethnically matched controls from India revealed several novel and disease-associated mutations (Govindaraj et al., 2014). However, in contrast to studies on other populations (Castro et al., 2006; Hagen et al., 2013), none of the mitochondrial haplogroup was found to be associated with HCM in India (Govindaraj et al., 2014). Christiansen et al. (in press) have reanalyzed this data by combining M, N, I and W haplogroups (as early cluster) and R, U and H haplogroups (as late cluster), and suggested that these two clusters of haplogroups were significantly different between HCM patients and controls. Hence, they proposed that mitochondrial haplogroups are associated with HCM in the Indian population. This analysis has the following issues: 1. samples with N, I, W (early cluster) and H (late cluster) haplogroups are very less in number (please refer to Table 1 of Christiansen et al., 2014); hence inclusion of such a low sample numbers would introduce bias; 2. p-values were not subjected to Bonferroni correction. Since more than one haplogroup was considered for the analysis, it is appropriate to correct the p-values with Bonferroni correction. Even with the inclusion of early and late cluster haplogroups, when Bonferroni corrections were applied to the p-values, obtained by Christiansen et al. (2014), we found that both early (p = 0.092) and late (p = 0.069) haplogroups are not significantly associated with HCM in the Indian population (Table 1). We once again reiterate that mitochondrial haplogroup, either independently or in combination, is not associated with HCM in India.

Neuroscience Research, 2009

s S39 endoplasmic reticulum to the Golgi, was observed. Because the mutant mouse of the mammalian... more s S39 endoplasmic reticulum to the Golgi, was observed. Because the mutant mouse of the mammalian yata orthologue, NTKL/SCYL1, shows spinocerebellar neurodegeneration, yata-dependent regulation of protein trafficking seems to be a conserved mechanism that is required for the neural homeostasis. doi:10.1016/j.neures.2009.09.028 O1-G3-4 Possible mutual interaction between diabetes mellitus and Alzheimer disease: Generation of novel transgenic mice models of Alzheimer disease with diabetic conditions Shuko Takeda1,2, Naoyuki Sato1,2, Kozue Uchio-Yamada3, Kyoko Sawada3, Takanori Kunieda3, Hiromi Rakugi2, Ryuichi Morishita1 1 Dept. Clinical Gene Therapy, Osaka University, Osaka, Japan; 2 Dept. Geriatric Medicine, Osaka University, Osaka, Japan; 3 Laboratory of Experimental Animal Models, National Institute of Biomedical Innovation, Osaka, Japan Recent studies suggest that diabetes mellitus is a risk factor for Alzheimer disease (AD). However, the underlying mechanisms are not clear. We generated two types of tg mice which show pathological conditions of both diseases (APP-ob/ob and APPNSY mice), and characterized their phenotypes. APP-ob/ob mice developed marked glucose intolerance and showed very early manifestation of memory impairment. APP-NSY mice also showed early manifestation of cognitive dysfunction at the age of 3 months. Exacerbation of memory impairment without an increase in Abeta load in these diabetic APP-Tg implies the role of diabetic conditions on Abeta-mediated neuronal dysfunction. Moreover, our findings also suggest the possibility that AD pathology could exacerbate metabolic phenotypes of diabetes. doi:10.1016/j.neures.2009.09.029 O1-G4-1 A search for genomic regions associated with neurodevelopmental differences between Rett syndrome monozygotic twins by genomic and epigenomic comparative assays Kenta Ohori1, Chunshu Yang1, Yusuke Miyanari2, Hidenori Sato3, Kazushi Endoh1, Mitsuru Emi3, Hiroyuki Sasaki2, Takeo Kubota1 1 Dept. Epigenet Med., Univ. Yamanashi, Japan; 2 Hum Genet, Natl. Inst. Genet, Japan; 3 DNA Chip Research Inc, Japan Rett syndrome (RTT) is a X-linked neurodevelopmental disorder caused by mutations in MECP2 gene. We here reported 7-year-old monozygotic RTT twins with noticeable clinical differences in development. To search genetic factors for these clinical differences, we examined MECP2 mutation, X-chromosome inactivation patterns, and DNA-methylation patterns of the MeCP2-target neuronal genes (BDNF and DLX5), but we did not find differences between the twins. Therefore, we currently investigate DNA-methylation patterns in unidentified MeCP2-target genes between the twins using genome microarray. We also investigated gene copy number variations (CNVs; variable regions in human genome) using genome microarray, and identified differences in 101 CNV regions between the twins. These epigenetic and genetic approaches will reveal susceptible genomic regions, encompassing neuronal genes, to neurodevelopmental disorders (e.g. autism). doi:10.1016/j.neures.2009.09.030 O1-G4-2 X11L protein deficiency is associated with the selective impairment of motivated approach behavior and the withdrawn response to social conflict Yoshitake Sano1, Veravej G. Ornthanalai1, Kazuyuki Yamada1, Chihiro Homma1, Hitomi Suzuki1, Toshiharu Suzuki2, Niall P. Murphy1, Shigeyoshi Itohara1 1 RIKEN BSI, Japan; 2 Hokkaido University Pharm., Japan Understanding how conflicting emotions are regulated is a crucial challenge in brain research. Model animals showing selective emotion-related phenotypes are highly useful for examining this issue. X11L is a neuronal adapter protein. X11L-KO mice were subordinate under competitive conditions, and showed decreased intruder exploration behavior in a resident-intruder test. Moreover, X11L-KO mice displayed defective ethological responses to attractive stimuli, in marble-burying, digging and burrowing tests. In contrast, X11L-KO mice were indistinguishable from wild-type mice in anxiety-like behaviors as determined by avoidance of unpleasant stimuli in open field, elevated plus maze, and light/dark transition tests. The abnormal behaviors in X11L-KO mice were rescued by the expression of X11L in forebrain regions during development. These findings suggest that X11L is involved in the development of neuronal circuits that contribute to conflict resolution. doi:10.1016/j.neures.2009.09.031 O1-G4-3 Genetic and clinical heterogeneity of mito-neuromuscular diseases in India Govindaraj Periyasamy1,2,3,4,5,6, Nahid A. Khan1, A. Vanniarajan1, U. Megha2, C. Sundaram2, A.K. Meena2, N. Gayathri3, Richa Singh1, N. Dinesh4, G.P. Rajshekher5, E.M. Elango6, Lalji Singh1, K. Thangaraj1 1 CCMB, Hyderabad, India; 2 NIMS, Hyderabad, India; 3 NIMHANS, Bangalore, India; 4 KMCH, Coimbatore, India; 5 SCTIMS, Trivandrum, India; 6 AIMS, Cochin, India We have sequenced the complete mtDNA of 365 clinically diagnosed individuals having definite neuromuscular(NM) symptoms that includes, CPEO,…

Investigative Opthalmology & Visual Science, 2013

PURPOSE. To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of India... more PURPOSE. To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber hereditary optic neuropathy (LHON) patients carrying the m.14484T>C mutation. METHODS. Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants. RESULTS. In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male:female ¼ 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e., F1c1, M31a, U2a, M*, I1, M6, M3a1, and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON. CONCLUSIONS. Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease.

Mitochondrion, 2011

We performed an extensive study on mitochondrial dysfunction in chronic periodontitis (CP). Elect... more We performed an extensive study on mitochondrial dysfunction in chronic periodontitis (CP). Electron microscopic analysis of gingival cells revealed abnormal mitochondria in 60% of the patients. Mitochondrial membrane potential and oxygen consumption of gingival cells were reduced by 4 fold and 5.8 fold, respectively; whereas ROS production was increased by 18%. The genetic analysis by complete mitochondrial DNA sequencing revealed the identification of 14 novel mutations only in periodontal tissues but not in the blood, suggesting a role of oxidative stress on periodontal tissues. Thus, our functional and genetic analysis provided an evidence for the mitochondrial dysfunction in CP.

International Journal of Clinical and Experimental Physiology, 2021

Background and Aim: Polycystic ovary syndrome (PCOS) and thyroid disorders are commonest endocrin... more Background and Aim: Polycystic ovary syndrome (PCOS) and thyroid disorders are commonest endocrine disorders; both of these disorders have profound effect on reproductive function in women's. An increase in ovarian volume and cystic changes in ovaries have been reported in hypothyroidism. Recent studies reveal that PCOS might be associated with cardiovascular autonomic dysfunction and the thyroid hormone also influences the autonomic nervous system. So the aim of the study was to first, evaluate and compare autonomic function in PCOS as well as in PCOS with hypothyroidism, second, correlation between thyroid stimulating hormone (TSH) and autonomic function tests (AFT) in both the groups and third, study also provided further exploration in autonomic function in PCOS in presence of hypothyroidism. Methods: Total 43 newly diagnosed not on medications subjects were recruited, these subjects were divided into group A PCOS (n=33) and group B PCOS with hypothyroidism (n=10). Anthropometric measurements were taken from all the participants and autonomic function tests for assessing parasympathetic function (such as heart rate response to immediate standing and standing to lying ratio) and sympathetic function (such as blood pressure response to immediate standing and mental arithmetic stress test) were employed, then measurements was taken according to the respective scoring procedures. Results: In our studied population PCOS as well as PCOS with hypothyroidism showed autonomic dysfunction but no significant difference was found between them. No correlation and significance was found between TSH and AFT in both the groups. Conclusion: Our study concluded that the presence of hypothyroidism did not further affect autonomic function in PCOS and TSH was unrelated to AFT.

International Journal of Clinical and Experimental Physiology, 2015

Reports on autonomic dysfunction associated with obesity in adolescent population are limited and... more Reports on autonomic dysfunction associated with obesity in adolescent population are limited and also are conflicting. Therefore in the present study, we have evaluated the difference in autonomic function between the obese and nonobese adolescents. Sixty-five adolescent subjects aged between 17 and 19 years were selected from HAHC Hospital, Jamia Hamdard. Based on their body mass index, these subjects were divided into a nonobese group (n = 54) and obese group (n = 11). Autonomic function tests for assessing parasympathetic function (such as heart rate response to immediate standing and standing to lying ratio) and sympathetic function (such as blood pressure response to immediate standing and cold pressor test) were employed. There was no difference in sympathetic and parasympathetic function between the obese and nonobese adolescents. Therefore, the findings of the present study suggest that the autonomic dysfunction was not statistically significant in the studied adolescent population.

Indian Journal of Medical Research, 2015

Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical pres... more Mitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.

Neuropediatrics, 2015

Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene (MT... more Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene (MT-ND5) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G > A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A > G mutation had episodic regression, progressive ataxia, optic atrophy, and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate, and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic-genetic testing and prognostication.

Mitochondrion, 2015

Complete mitochondrial DNA (mtDNA) analysis of 114 HCM patients along with 300 ethnically matched... more Complete mitochondrial DNA (mtDNA) analysis of 114 HCM patients along with 300 ethnically matched controls from India revealed several novel and disease-associated mutations (Govindaraj et al., 2014). However, in contrast to studies on other populations (Castro et al., 2006; Hagen et al., 2013), none of the mitochondrial haplogroup was found to be associated with HCM in India (Govindaraj et al., 2014). Christiansen et al. (in press) have reanalyzed this data by combining M, N, I and W haplogroups (as early cluster) and R, U and H haplogroups (as late cluster), and suggested that these two clusters of haplogroups were significantly different between HCM patients and controls. Hence, they proposed that mitochondrial haplogroups are associated with HCM in the Indian population. This analysis has the following issues: 1. samples with N, I, W (early cluster) and H (late cluster) haplogroups are very less in number (please refer to Table 1 of Christiansen et al., 2014); hence inclusion of such a low sample numbers would introduce bias; 2. p-values were not subjected to Bonferroni correction. Since more than one haplogroup was considered for the analysis, it is appropriate to correct the p-values with Bonferroni correction. Even with the inclusion of early and late cluster haplogroups, when Bonferroni corrections were applied to the p-values, obtained by Christiansen et al. (2014), we found that both early (p = 0.092) and late (p = 0.069) haplogroups are not significantly associated with HCM in the Indian population (Table 1). We once again reiterate that mitochondrial haplogroup, either independently or in combination, is not associated with HCM in India.

Neuroscience Research, 2009

s S39 endoplasmic reticulum to the Golgi, was observed. Because the mutant mouse of the mammalian... more s S39 endoplasmic reticulum to the Golgi, was observed. Because the mutant mouse of the mammalian yata orthologue, NTKL/SCYL1, shows spinocerebellar neurodegeneration, yata-dependent regulation of protein trafficking seems to be a conserved mechanism that is required for the neural homeostasis. doi:10.1016/j.neures.2009.09.028 O1-G3-4 Possible mutual interaction between diabetes mellitus and Alzheimer disease: Generation of novel transgenic mice models of Alzheimer disease with diabetic conditions Shuko Takeda1,2, Naoyuki Sato1,2, Kozue Uchio-Yamada3, Kyoko Sawada3, Takanori Kunieda3, Hiromi Rakugi2, Ryuichi Morishita1 1 Dept. Clinical Gene Therapy, Osaka University, Osaka, Japan; 2 Dept. Geriatric Medicine, Osaka University, Osaka, Japan; 3 Laboratory of Experimental Animal Models, National Institute of Biomedical Innovation, Osaka, Japan Recent studies suggest that diabetes mellitus is a risk factor for Alzheimer disease (AD). However, the underlying mechanisms are not clear. We generated two types of tg mice which show pathological conditions of both diseases (APP-ob/ob and APPNSY mice), and characterized their phenotypes. APP-ob/ob mice developed marked glucose intolerance and showed very early manifestation of memory impairment. APP-NSY mice also showed early manifestation of cognitive dysfunction at the age of 3 months. Exacerbation of memory impairment without an increase in Abeta load in these diabetic APP-Tg implies the role of diabetic conditions on Abeta-mediated neuronal dysfunction. Moreover, our findings also suggest the possibility that AD pathology could exacerbate metabolic phenotypes of diabetes. doi:10.1016/j.neures.2009.09.029 O1-G4-1 A search for genomic regions associated with neurodevelopmental differences between Rett syndrome monozygotic twins by genomic and epigenomic comparative assays Kenta Ohori1, Chunshu Yang1, Yusuke Miyanari2, Hidenori Sato3, Kazushi Endoh1, Mitsuru Emi3, Hiroyuki Sasaki2, Takeo Kubota1 1 Dept. Epigenet Med., Univ. Yamanashi, Japan; 2 Hum Genet, Natl. Inst. Genet, Japan; 3 DNA Chip Research Inc, Japan Rett syndrome (RTT) is a X-linked neurodevelopmental disorder caused by mutations in MECP2 gene. We here reported 7-year-old monozygotic RTT twins with noticeable clinical differences in development. To search genetic factors for these clinical differences, we examined MECP2 mutation, X-chromosome inactivation patterns, and DNA-methylation patterns of the MeCP2-target neuronal genes (BDNF and DLX5), but we did not find differences between the twins. Therefore, we currently investigate DNA-methylation patterns in unidentified MeCP2-target genes between the twins using genome microarray. We also investigated gene copy number variations (CNVs; variable regions in human genome) using genome microarray, and identified differences in 101 CNV regions between the twins. These epigenetic and genetic approaches will reveal susceptible genomic regions, encompassing neuronal genes, to neurodevelopmental disorders (e.g. autism). doi:10.1016/j.neures.2009.09.030 O1-G4-2 X11L protein deficiency is associated with the selective impairment of motivated approach behavior and the withdrawn response to social conflict Yoshitake Sano1, Veravej G. Ornthanalai1, Kazuyuki Yamada1, Chihiro Homma1, Hitomi Suzuki1, Toshiharu Suzuki2, Niall P. Murphy1, Shigeyoshi Itohara1 1 RIKEN BSI, Japan; 2 Hokkaido University Pharm., Japan Understanding how conflicting emotions are regulated is a crucial challenge in brain research. Model animals showing selective emotion-related phenotypes are highly useful for examining this issue. X11L is a neuronal adapter protein. X11L-KO mice were subordinate under competitive conditions, and showed decreased intruder exploration behavior in a resident-intruder test. Moreover, X11L-KO mice displayed defective ethological responses to attractive stimuli, in marble-burying, digging and burrowing tests. In contrast, X11L-KO mice were indistinguishable from wild-type mice in anxiety-like behaviors as determined by avoidance of unpleasant stimuli in open field, elevated plus maze, and light/dark transition tests. The abnormal behaviors in X11L-KO mice were rescued by the expression of X11L in forebrain regions during development. These findings suggest that X11L is involved in the development of neuronal circuits that contribute to conflict resolution. doi:10.1016/j.neures.2009.09.031 O1-G4-3 Genetic and clinical heterogeneity of mito-neuromuscular diseases in India Govindaraj Periyasamy1,2,3,4,5,6, Nahid A. Khan1, A. Vanniarajan1, U. Megha2, C. Sundaram2, A.K. Meena2, N. Gayathri3, Richa Singh1, N. Dinesh4, G.P. Rajshekher5, E.M. Elango6, Lalji Singh1, K. Thangaraj1 1 CCMB, Hyderabad, India; 2 NIMS, Hyderabad, India; 3 NIMHANS, Bangalore, India; 4 KMCH, Coimbatore, India; 5 SCTIMS, Trivandrum, India; 6 AIMS, Cochin, India We have sequenced the complete mtDNA of 365 clinically diagnosed individuals having definite neuromuscular(NM) symptoms that includes, CPEO,…

Investigative Opthalmology & Visual Science, 2013

PURPOSE. To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of India... more PURPOSE. To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber hereditary optic neuropathy (LHON) patients carrying the m.14484T>C mutation. METHODS. Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants. RESULTS. In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male:female ¼ 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e., F1c1, M31a, U2a, M*, I1, M6, M3a1, and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON. CONCLUSIONS. Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease.

Mitochondrion, 2011

We performed an extensive study on mitochondrial dysfunction in chronic periodontitis (CP). Elect... more We performed an extensive study on mitochondrial dysfunction in chronic periodontitis (CP). Electron microscopic analysis of gingival cells revealed abnormal mitochondria in 60% of the patients. Mitochondrial membrane potential and oxygen consumption of gingival cells were reduced by 4 fold and 5.8 fold, respectively; whereas ROS production was increased by 18%. The genetic analysis by complete mitochondrial DNA sequencing revealed the identification of 14 novel mutations only in periodontal tissues but not in the blood, suggesting a role of oxidative stress on periodontal tissues. Thus, our functional and genetic analysis provided an evidence for the mitochondrial dysfunction in CP.