ABSTRACT Intellectual and developmental disabilities are the most common neurological problem aff... more ABSTRACT Intellectual and developmental disabilities are the most common neurological problem affecting 1-3% of the world population. Cognitive impairment along with neuromotor dysfunction is also frequently associated with Down syndrome. Influence of dopaminergic neurotransmission on cognition is well known. Monoamine oxidase A (MAOA) and Catechol-O-methyl transferase (COMT) play important regulatory roles in maintaining the level of dopamine. In the present investigation, a polymorphic allele in the MAOA gene (MAOA-u VNTR) and a bimorphic polymorphism Val158Met (rs 4680) in COMT have been analyzed in subjects suffering from various levels of intellectual disability. Intellectually challenged individuals were recruited following the criteria mentioned by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and classified based on the intelligent quotient (IQ). Control individuals belonging to the same ethnic group were also recruited after evaluation. Peripheral blood was collected, after obtaining informed written consent, for isolation of genomic DNA to be used for PCR-based amplification of target sites and analysis. No significant contribution of the COMT Val158Met was observed by both case-control and family-based association methods. The MAOA-u VNTR also failed to show any significant difference between the control and intellectually challenged subjects. However, a trend towards association with the shorter repeats of the MAOA-u VNTR was noticed in a sub-group of intellectually disabled people with aggressive behavior (p<0.05). For the first time, association of these polymorphisms in individuals with intellectual disability have been explored and the data obtained revealed significant contribution of the MAOA-u VNTR in the behavioral attributes of intellectually challenged individuals.
Down Syndrome (DS) is a well known genetic disorder with several co-morbid conditions like hypoto... more Down Syndrome (DS) is a well known genetic disorder with several co-morbid conditions like hypotonia, depression, irritability, early onset Alzheimer disease, mental retardation, etc. Cognitive dysfunction is a common feature associated with DS and a hypodopaminergic state has been assumed to be responsible for the phenotype. Function of dopamine is mediated through a group of receptors and amongst the five receptors, D1-D5, an increased number of the D4 receptor is known to be expressed in regions of the brain involved in cognition. A repeat polymorphism (2-7 repeat units of 48 bp) in the exon 3 of DRD4 gene has been found to be associated with different psychiatric and neurobehavioral disorders. In the present investigation, we have explored the association of DRD4 exon 3 polymorphism with DS. Diagnosis was carried out by mental health professionals following DSM-IV criteria and confirmed by chromosomal analysis. Alleles were grouped as A1 (2, 3, 4 repeats) and A2 (5, 6, 7 repeats...
Cognitive impairment along with neuro-motor dysfunction is commonly observed in mentally retarded... more Cognitive impairment along with neuro-motor dysfunction is commonly observed in mentally retarded individuals, be it idiopathic mental retardation (MR) or Down syndrome (DS). Influence of catecholaminergic neurotransmission on cognition is well known and Monoamine oxidase A (MAOA) is believed to play a key role in cognition. A promoter polymorphism in the MAOA gene with short (≤ 3 repeat units) and long (≥4 repeat units) alleles have been reported in association with neuropsychiatric disorders. This is the first population-based study on MAOA-u VNTR in association with MR and DS. Genotypic frequencies of MR cases did not show any significant difference with that of control. Family-based association analysis also failed to show any relation with MR. On the other hand, genotypic frequencies of DS cases were significantly different as compared to controls and by family-based association analysis, a significant bias in transmission of the long 4.5 repeat allele to DS probands, in partic...
Intellectual disability (ID) is the most common problem associated with cognitive impairment and ... more Intellectual disability (ID) is the most common problem associated with cognitive impairment and neuromotor dysfunctions and severity of the disorder is evaluated on the bases of intelligence quotient (IQ). Dopamine (DA) plays an important role in the regulation of frontal cortex which controls cognition and movement and the level is maintained by enzymes like Monoamine oxidase A (MAOA), Catechol-O-methyl transferase (COMT) and mediated through Dopamine receptor D4 (DRD4). Functional genetic polymorphisms have a potency to alter the roles played by these proteins and hence forth, in the present investigation different functional polymorphisms in the MAOA (MAOA-u VNTR and rs6323), COMT (rs4680) and DRD4 (exon3 VNTR and rs1800955) genes have been analyzed in subjects suffering from ID. Subjects were recruited following the criteria of DSM-IV and classified on the bases of IQ. Control individuals belonging to same ethnic group were also recruited after evaluation. After obtaining infor...
Objective Dopamine (DA), the major neurotransmitter, is essential for attention, cognition and se... more Objective Dopamine (DA), the major neurotransmitter, is essential for attention, cognition and several other physiological activities which are mostly impaired in Attention Deficit Hyperactivity Disorder (ADHD) subjects. A number of investigators throughout the world have shown association of different dopaminergic genes, mainly receptors and transporters, with ADHD. The present study was designed to explore association of cognitive deficit and hyperactivity, two common traits of ADHD probands, with variants in the DA receptor 2 (DRD2), receptor 4 (DRD4) and transporter (DAT1) genes. Method ADHD probands (N=128) and ethnically matched controls (N=120) were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Conners parents/teachers rating scale was used to measure cognitive deficit and hyperactivity. Peripheral blood collected was used for isolation of genomic DNA after obtaining informed written consent. To analyze functionally significant gene varian...
Background: Engrailed 2 (EN2) is located on chromosome 7q36.3, a genomic region linked to ASD and... more Background: Engrailed 2 (EN2) is located on chromosome 7q36.3, a genomic region linked to ASD and developmental language disorder, and has been implicated in the patterning of cerebellum during development. Studies on En2-/- mice indicate the role of En2 in midbrain and cerebellum development as these mice display cerebellar hypoplasia, reduction in Purkinje cells with markedly reduced cerebellum and alterations in cerebellar serotonin levels. They also show impaired motor learning in the rotarod and complex socio-behavioral changes. Such deficits are reminiscent of symptoms observed in autistic individuals. Engrailed genes are necessary for serotonergic neuron development and defects in the serotoninergic system have been implicated in autism. Therefore, EN2 is considered a candidate gene for autism. Objectives: The main focus is to investigate genetic association of EN2 with autism in the Indian population. Methods: Autistic probands were recruited following DSM-IV criteria and CA...
The International Journal of Biological Markers, 2014
Thyroid malfunction is more common in individuals with Down syndrome (DS) than in the general pop... more Thyroid malfunction is more common in individuals with Down syndrome (DS) than in the general population. It has been hypothesized that thyroid may influence cancer risk. Individuals with DS are at greater risk of developing leukemia than the general population, while solid tumors especially breast cancer (BC) are rare. BC patients have higher levels of circulating thyroid-stimulating hormone (TSH) and prolactin (PRL), both regulated by the thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide. This study was aimed at investigating the status of TRH functional polymorphisms in subjects with DS and BC. Unrelated families with DS probands (n=180), individuals with BC (n=99) and ethnically matched controls (n=216) were recruited. Genomic DNA isolated from peripheral blood was subjected to PCR amplification followed by DNA sequence analysis. Data obtained were analyzed by population- and family-based statistical analysis. Among 30 studied sites, only 2 (rs7645772 and rs13097335...
Engrailed 2 (EN2) is a homeobox transcription factor involved in the patterning of cerebellum dur... more Engrailed 2 (EN2) is a homeobox transcription factor involved in the patterning of cerebellum during brain development. Linkage analysis and studies on knockout mice support EN2, located on chromosome 7q36.3, as a potential risk locus for autism. Candidate gene approach also suggested association of EN2 with autism spectrum disorder (ASD) in various populations. Here, we have investigated the association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/‐) and rs6150410 (CGCATCCCC/‐) in promoter region; rs1861972 (A/G) and rs1861973 (C/T) in the intron] of the gene with autism and ASD in Indian population using family‐based approach. Probands have been recruited using Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM‐IV) diagnostic criteria. Genotypic distributions conform to Hardy–Weinberg equilibrium. Genotyping analysis showed that the intronic single nucleotide polymorphisms (SNPs) are in complete linkage disequilibrium showing A‐C and correspond...
Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early br... more Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early brain developmental abnormalities involving neuronal migration and lamination are implicated in childhood epilepsy. Reelin, a neuronal-signaling molecule plays a crucial role in these migratory processes. Therefore, reelin gene (RELN), which is located on human chromosome 7q22 is considered as a potential candidate gene for childhood epilepsy. In this study, we recruited 63 patients with childhood-onset epilepsy and 103 healthy controls from West Bengal in India. Genomic DNA isolated from leukocytes of cases and control individuals were used for genotyping analysis of 16 markers of RELN. Case-control analysis revealed significant over-representation of G/C and (G/C+C/C) genotypes, and C allele of exon 22 G/C marker (rs362691) in cases as compared to controls. Pair-wise linkage disequilibrium analysis demonstrated two separate LD blocks with moderately high D' values in epileptic cases. Based on these data, we have carried out haplotype case-control analysis. Even though we found over-representation of A-C haplotype of intron 12 A/C/exon 22 G/C markers and haplotype combination involving G-allele of exon 22 marker in cases and controls, respectively, the overall test was not significant. LD in this region involving this marker was also more robust in epileptic cases. Taken together, the results provide possible evidences for association of exon 22 G/C marker or any marker in the vicinity, which is in LD with this marker with epilepsy in the West Bengal population. Further investigations involving higher sample sizes are warranted to validate the present finding.
... How to cite this article : DAS B ,DUTTA S,CHATTERJEE A,SINHA S,CHATTOPADHYAY A,MUKHOPADHYAY K... more ... How to cite this article : DAS B ,DUTTA S,CHATTERJEE A,SINHA S,CHATTOPADHYAY A,MUKHOPADHYAY K. . SCREENING ... who attended the psychiatric out-patient department for various neurobehavioural disorders like autism , spectrum disorder (ASD), epilepsy, attention ...
ABSTRACT Intellectual and developmental disabilities are the most common neurological problem aff... more ABSTRACT Intellectual and developmental disabilities are the most common neurological problem affecting 1-3% of the world population. Cognitive impairment along with neuromotor dysfunction is also frequently associated with Down syndrome. Influence of dopaminergic neurotransmission on cognition is well known. Monoamine oxidase A (MAOA) and Catechol-O-methyl transferase (COMT) play important regulatory roles in maintaining the level of dopamine. In the present investigation, a polymorphic allele in the MAOA gene (MAOA-u VNTR) and a bimorphic polymorphism Val158Met (rs 4680) in COMT have been analyzed in subjects suffering from various levels of intellectual disability. Intellectually challenged individuals were recruited following the criteria mentioned by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and classified based on the intelligent quotient (IQ). Control individuals belonging to the same ethnic group were also recruited after evaluation. Peripheral blood was collected, after obtaining informed written consent, for isolation of genomic DNA to be used for PCR-based amplification of target sites and analysis. No significant contribution of the COMT Val158Met was observed by both case-control and family-based association methods. The MAOA-u VNTR also failed to show any significant difference between the control and intellectually challenged subjects. However, a trend towards association with the shorter repeats of the MAOA-u VNTR was noticed in a sub-group of intellectually disabled people with aggressive behavior (p<0.05). For the first time, association of these polymorphisms in individuals with intellectual disability have been explored and the data obtained revealed significant contribution of the MAOA-u VNTR in the behavioral attributes of intellectually challenged individuals.
Down Syndrome (DS) is a well known genetic disorder with several co-morbid conditions like hypoto... more Down Syndrome (DS) is a well known genetic disorder with several co-morbid conditions like hypotonia, depression, irritability, early onset Alzheimer disease, mental retardation, etc. Cognitive dysfunction is a common feature associated with DS and a hypodopaminergic state has been assumed to be responsible for the phenotype. Function of dopamine is mediated through a group of receptors and amongst the five receptors, D1-D5, an increased number of the D4 receptor is known to be expressed in regions of the brain involved in cognition. A repeat polymorphism (2-7 repeat units of 48 bp) in the exon 3 of DRD4 gene has been found to be associated with different psychiatric and neurobehavioral disorders. In the present investigation, we have explored the association of DRD4 exon 3 polymorphism with DS. Diagnosis was carried out by mental health professionals following DSM-IV criteria and confirmed by chromosomal analysis. Alleles were grouped as A1 (2, 3, 4 repeats) and A2 (5, 6, 7 repeats...
Cognitive impairment along with neuro-motor dysfunction is commonly observed in mentally retarded... more Cognitive impairment along with neuro-motor dysfunction is commonly observed in mentally retarded individuals, be it idiopathic mental retardation (MR) or Down syndrome (DS). Influence of catecholaminergic neurotransmission on cognition is well known and Monoamine oxidase A (MAOA) is believed to play a key role in cognition. A promoter polymorphism in the MAOA gene with short (≤ 3 repeat units) and long (≥4 repeat units) alleles have been reported in association with neuropsychiatric disorders. This is the first population-based study on MAOA-u VNTR in association with MR and DS. Genotypic frequencies of MR cases did not show any significant difference with that of control. Family-based association analysis also failed to show any relation with MR. On the other hand, genotypic frequencies of DS cases were significantly different as compared to controls and by family-based association analysis, a significant bias in transmission of the long 4.5 repeat allele to DS probands, in partic...
Intellectual disability (ID) is the most common problem associated with cognitive impairment and ... more Intellectual disability (ID) is the most common problem associated with cognitive impairment and neuromotor dysfunctions and severity of the disorder is evaluated on the bases of intelligence quotient (IQ). Dopamine (DA) plays an important role in the regulation of frontal cortex which controls cognition and movement and the level is maintained by enzymes like Monoamine oxidase A (MAOA), Catechol-O-methyl transferase (COMT) and mediated through Dopamine receptor D4 (DRD4). Functional genetic polymorphisms have a potency to alter the roles played by these proteins and hence forth, in the present investigation different functional polymorphisms in the MAOA (MAOA-u VNTR and rs6323), COMT (rs4680) and DRD4 (exon3 VNTR and rs1800955) genes have been analyzed in subjects suffering from ID. Subjects were recruited following the criteria of DSM-IV and classified on the bases of IQ. Control individuals belonging to same ethnic group were also recruited after evaluation. After obtaining infor...
Objective Dopamine (DA), the major neurotransmitter, is essential for attention, cognition and se... more Objective Dopamine (DA), the major neurotransmitter, is essential for attention, cognition and several other physiological activities which are mostly impaired in Attention Deficit Hyperactivity Disorder (ADHD) subjects. A number of investigators throughout the world have shown association of different dopaminergic genes, mainly receptors and transporters, with ADHD. The present study was designed to explore association of cognitive deficit and hyperactivity, two common traits of ADHD probands, with variants in the DA receptor 2 (DRD2), receptor 4 (DRD4) and transporter (DAT1) genes. Method ADHD probands (N=128) and ethnically matched controls (N=120) were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Conners parents/teachers rating scale was used to measure cognitive deficit and hyperactivity. Peripheral blood collected was used for isolation of genomic DNA after obtaining informed written consent. To analyze functionally significant gene varian...
Background: Engrailed 2 (EN2) is located on chromosome 7q36.3, a genomic region linked to ASD and... more Background: Engrailed 2 (EN2) is located on chromosome 7q36.3, a genomic region linked to ASD and developmental language disorder, and has been implicated in the patterning of cerebellum during development. Studies on En2-/- mice indicate the role of En2 in midbrain and cerebellum development as these mice display cerebellar hypoplasia, reduction in Purkinje cells with markedly reduced cerebellum and alterations in cerebellar serotonin levels. They also show impaired motor learning in the rotarod and complex socio-behavioral changes. Such deficits are reminiscent of symptoms observed in autistic individuals. Engrailed genes are necessary for serotonergic neuron development and defects in the serotoninergic system have been implicated in autism. Therefore, EN2 is considered a candidate gene for autism. Objectives: The main focus is to investigate genetic association of EN2 with autism in the Indian population. Methods: Autistic probands were recruited following DSM-IV criteria and CA...
The International Journal of Biological Markers, 2014
Thyroid malfunction is more common in individuals with Down syndrome (DS) than in the general pop... more Thyroid malfunction is more common in individuals with Down syndrome (DS) than in the general population. It has been hypothesized that thyroid may influence cancer risk. Individuals with DS are at greater risk of developing leukemia than the general population, while solid tumors especially breast cancer (BC) are rare. BC patients have higher levels of circulating thyroid-stimulating hormone (TSH) and prolactin (PRL), both regulated by the thyrotropin-releasing hormone (TRH), a hypothalamic tripeptide. This study was aimed at investigating the status of TRH functional polymorphisms in subjects with DS and BC. Unrelated families with DS probands (n=180), individuals with BC (n=99) and ethnically matched controls (n=216) were recruited. Genomic DNA isolated from peripheral blood was subjected to PCR amplification followed by DNA sequence analysis. Data obtained were analyzed by population- and family-based statistical analysis. Among 30 studied sites, only 2 (rs7645772 and rs13097335...
Engrailed 2 (EN2) is a homeobox transcription factor involved in the patterning of cerebellum dur... more Engrailed 2 (EN2) is a homeobox transcription factor involved in the patterning of cerebellum during brain development. Linkage analysis and studies on knockout mice support EN2, located on chromosome 7q36.3, as a potential risk locus for autism. Candidate gene approach also suggested association of EN2 with autism spectrum disorder (ASD) in various populations. Here, we have investigated the association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/‐) and rs6150410 (CGCATCCCC/‐) in promoter region; rs1861972 (A/G) and rs1861973 (C/T) in the intron] of the gene with autism and ASD in Indian population using family‐based approach. Probands have been recruited using Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM‐IV) diagnostic criteria. Genotypic distributions conform to Hardy–Weinberg equilibrium. Genotyping analysis showed that the intronic single nucleotide polymorphisms (SNPs) are in complete linkage disequilibrium showing A‐C and correspond...
Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early br... more Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early brain developmental abnormalities involving neuronal migration and lamination are implicated in childhood epilepsy. Reelin, a neuronal-signaling molecule plays a crucial role in these migratory processes. Therefore, reelin gene (RELN), which is located on human chromosome 7q22 is considered as a potential candidate gene for childhood epilepsy. In this study, we recruited 63 patients with childhood-onset epilepsy and 103 healthy controls from West Bengal in India. Genomic DNA isolated from leukocytes of cases and control individuals were used for genotyping analysis of 16 markers of RELN. Case-control analysis revealed significant over-representation of G/C and (G/C+C/C) genotypes, and C allele of exon 22 G/C marker (rs362691) in cases as compared to controls. Pair-wise linkage disequilibrium analysis demonstrated two separate LD blocks with moderately high D' values in epileptic cases. Based on these data, we have carried out haplotype case-control analysis. Even though we found over-representation of A-C haplotype of intron 12 A/C/exon 22 G/C markers and haplotype combination involving G-allele of exon 22 marker in cases and controls, respectively, the overall test was not significant. LD in this region involving this marker was also more robust in epileptic cases. Taken together, the results provide possible evidences for association of exon 22 G/C marker or any marker in the vicinity, which is in LD with this marker with epilepsy in the West Bengal population. Further investigations involving higher sample sizes are warranted to validate the present finding.
... How to cite this article : DAS B ,DUTTA S,CHATTERJEE A,SINHA S,CHATTOPADHYAY A,MUKHOPADHYAY K... more ... How to cite this article : DAS B ,DUTTA S,CHATTERJEE A,SINHA S,CHATTOPADHYAY A,MUKHOPADHYAY K. . SCREENING ... who attended the psychiatric out-patient department for various neurobehavioural disorders like autism , spectrum disorder (ASD), epilepsy, attention ...
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