Pub Date : 2021-12-01DOI: 10.1097/YPG.0000000000000301
Muhammed Furkan Erbay, Ali Karayağmurlu
Etiopathogenesis of autism spectrum disorder (ASD) is highly heterogeneous. Genetic factors play a major role in the etiology of ASD, and 16p11.2 microdeletion is one of the best-known genetic abnormalities thought to be strongly linked to ASD. Conversely, 17q12 microduplication is observed relatively rarely, yet it is reported that 17q12 recurrent duplication also results in a predisposition to ASD. Additionally, 16p11.2 microdeletion is characterized by developmental delay, intellectual disability, ASD and seizures, while 17q12 recurrent duplication is thought to be related to intellectual disability, seizures, eye or vision problems and, rarely, cardiac and renal anomalies. It also has been linked to ASD, schizophrenia, aggression and self-injury. This paper presents two different genetic abnormalities and their relations to ASD. Two siblings were studied; in one of the siblings, maternally originated 17q12 duplication was identified, and paternally originated 16p11.2 microdeletion was identified in the other sibling. To the best of the authors' knowledge, the present paper is a rare case report which shows the coexistence of 17q12 duplication, clubfoot deformity and ASD as well as 16p11.2 microdeletion, spina bifida occulta and ASD.
{"title":"Two siblings with autism spectrum disorder and two different genetic abnormalities: paternal 16p11.2 microdeletion and maternal 17q12 microduplication.","authors":"Muhammed Furkan Erbay, Ali Karayağmurlu","doi":"10.1097/YPG.0000000000000301","DOIUrl":"10.1097/YPG.0000000000000301","url":null,"abstract":"<p><p>Etiopathogenesis of autism spectrum disorder (ASD) is highly heterogeneous. Genetic factors play a major role in the etiology of ASD, and 16p11.2 microdeletion is one of the best-known genetic abnormalities thought to be strongly linked to ASD. Conversely, 17q12 microduplication is observed relatively rarely, yet it is reported that 17q12 recurrent duplication also results in a predisposition to ASD. Additionally, 16p11.2 microdeletion is characterized by developmental delay, intellectual disability, ASD and seizures, while 17q12 recurrent duplication is thought to be related to intellectual disability, seizures, eye or vision problems and, rarely, cardiac and renal anomalies. It also has been linked to ASD, schizophrenia, aggression and self-injury. This paper presents two different genetic abnormalities and their relations to ASD. Two siblings were studied; in one of the siblings, maternally originated 17q12 duplication was identified, and paternally originated 16p11.2 microdeletion was identified in the other sibling. To the best of the authors' knowledge, the present paper is a rare case report which shows the coexistence of 17q12 duplication, clubfoot deformity and ASD as well as 16p11.2 microdeletion, spina bifida occulta and ASD.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39429350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000281
Oluwagbenga Dada, Christopher Adanty, Nasia Dai, Clement Zai, Philip Gerretsen, Ariel Graff, Vincenzo de Luca
Stress is an important risk factor for suicidal ideation, but the mechanisms that link stress, suicidal ideation and neurobiology remain unclear. Epigenetic mechanisms are involved in both vulnerability to suicidal behavior and stress. This is a pilot study of 60 patients with schizophrenia spectrum disorders (36 men and 24 women), with an average age of 43.75 ± 12.24 years. We analyzed the effects of (1) perceived stress and (2) the mediation of genome-wide methylation (~450 000 CpG sites) on suicidal ideation severity. The top CpG site mediating the effect of stress on suicidal ideation was the cg10782349 located in the ZNF701 gene on chromosome 19, facilitating the effect through DNA hypermethylation. These preliminary results indicate that DNA methylation in peripheral tissues can clarify the complex relationship between stress and suicidal ideation in schizophrenia.
{"title":"Mediating effect of genome-wide DNA methylation on suicidal ideation induced by perceived stress.","authors":"Oluwagbenga Dada, Christopher Adanty, Nasia Dai, Clement Zai, Philip Gerretsen, Ariel Graff, Vincenzo de Luca","doi":"10.1097/YPG.0000000000000281","DOIUrl":"10.1097/YPG.0000000000000281","url":null,"abstract":"<p><p>Stress is an important risk factor for suicidal ideation, but the mechanisms that link stress, suicidal ideation and neurobiology remain unclear. Epigenetic mechanisms are involved in both vulnerability to suicidal behavior and stress. This is a pilot study of 60 patients with schizophrenia spectrum disorders (36 men and 24 women), with an average age of 43.75 ± 12.24 years. We analyzed the effects of (1) perceived stress and (2) the mediation of genome-wide methylation (~450 000 CpG sites) on suicidal ideation severity. The top CpG site mediating the effect of stress on suicidal ideation was the cg10782349 located in the ZNF701 gene on chromosome 19, facilitating the effect through DNA hypermethylation. These preliminary results indicate that DNA methylation in peripheral tissues can clarify the complex relationship between stress and suicidal ideation in schizophrenia.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38949201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000287
Robertas Strumila, Aiste Lengvenyte, Laima Ambrozaityte, Danute Balkeliene, Algirdas Utkus, Edgaras Dlugauskas
Background: The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype.
Methods: We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results.
Results: Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2 = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.
Conclusions: Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.
{"title":"CYP2C19 polymorphisms are associated with severity of depression at initial evaluation and after the treatment independently of the prescribed medications: 4 weeks prospective study.","authors":"Robertas Strumila, Aiste Lengvenyte, Laima Ambrozaityte, Danute Balkeliene, Algirdas Utkus, Edgaras Dlugauskas","doi":"10.1097/YPG.0000000000000287","DOIUrl":"10.1097/YPG.0000000000000287","url":null,"abstract":"<p><strong>Background: </strong>The cytochrome P-450 2C19 (CYP2C19) enzyme is involved in the metabolism of numerous antidepressants. It also metabolises some endogenous substrates, which could also confer to vulnerability. We aimed to establish whether the severity of depression and treatment response are associated with the genetically predicted CYP2C19 phenotype.</p><p><strong>Methods: </strong>We assessed the CYP2C19 genotype-predicted metabolic phenotypes (normal, intermediate or ultrarapid, there were no poor metabolisers) in patients with moderate or severe depression. We used the self-rated Beck Depression Inventory-II (BDI-II) scale and the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, after 2 and 4 weeks of an empirical treatment trial. Patients and clinicians were blind to the genetic testing results.</p><p><strong>Results: </strong>Seventy-six patients participated in the present study. At baseline, impaired CYP2C19 metabolisers, compared to normal metabolisers, had higher BDI-II (P = 0.046; ηp2 = 0.08) but not MADRS score. Intermediate metabolisers more often had a diagnosis of severe depression than normal metabolisers (P = 0.003). After 4 weeks of empirical treatment, intermediate metabolisers had significantly higher MADRS and BDI-II scores than normal metabolisers (P = 0.006; ηp2 = 0.131 and P = 0.030; ηp2 = 0.091). These differences were independent of the use of CYP2C19-metabolised medications in the treatment trial, as well as the treatment discrepancy status.</p><p><strong>Conclusions: </strong>Intermediate CYP2C19 polymorphism-predicted activity was associated with more severe depression after an empirical treatment trial. The lack of association between the prescription of CYP2C19-metabolised drugs and treatment response calls for a further look into the role of endogenous substrates of CYP2C19.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39236052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000294
Yorran Hardman Araújo Montenegro, Guilherme Baldo, Roberto Giugliani, Fabiano de Oliveira Poswar, Ruy Pires de Oliveira Sobrinho, Carlos Eduardo Steiner
Due to their low frequency and some atypical presentations, inborn errors of metabolism are frequently misdiagnosed or underdiagnosed, which hinders the correct management of these patients. To illustrate that, here we present a patient that, at early school age, had learning disabilities compared to her classmates, especially for writing. She completed basic education in a regular school and was transferred to a secondary school for students with special needs. At 18 years of age, she presented a first psychiatric abrupt outbreak: she spent a month screaming and without sleeping. Behavioral problems then became apparent, especially hyperactivity, destructive and chaotic behavior, anxiety, and auto-aggressivity and hetero-aggressivity. A diagnosis of schizophreniform disorder was established. Clinical genetic evaluation revealed coarse face, macroglossia, coarse thick hair, and mild hepatomegaly, and the hypothesis of mucopolysaccharidosis-III was raised. Laboratory tests indicated high levels of urinary glycosaminoglycans and almost undetectable NAGLU activity, confirming the diagnosis. Sequencing of the NAGLU gene revealed the c.1318G>C (p.Gly440Arg) and c.1834A>G (p.Ser612Gly) mutations.
{"title":"Schizophreniform presentation and abrupt neurologic decline in a patient with late-onset mucopolysaccharidosis type IIIB.","authors":"Yorran Hardman Araújo Montenegro, Guilherme Baldo, Roberto Giugliani, Fabiano de Oliveira Poswar, Ruy Pires de Oliveira Sobrinho, Carlos Eduardo Steiner","doi":"10.1097/YPG.0000000000000294","DOIUrl":"10.1097/YPG.0000000000000294","url":null,"abstract":"<p><p>Due to their low frequency and some atypical presentations, inborn errors of metabolism are frequently misdiagnosed or underdiagnosed, which hinders the correct management of these patients. To illustrate that, here we present a patient that, at early school age, had learning disabilities compared to her classmates, especially for writing. She completed basic education in a regular school and was transferred to a secondary school for students with special needs. At 18 years of age, she presented a first psychiatric abrupt outbreak: she spent a month screaming and without sleeping. Behavioral problems then became apparent, especially hyperactivity, destructive and chaotic behavior, anxiety, and auto-aggressivity and hetero-aggressivity. A diagnosis of schizophreniform disorder was established. Clinical genetic evaluation revealed coarse face, macroglossia, coarse thick hair, and mild hepatomegaly, and the hypothesis of mucopolysaccharidosis-III was raised. Laboratory tests indicated high levels of urinary glycosaminoglycans and almost undetectable NAGLU activity, confirming the diagnosis. Sequencing of the NAGLU gene revealed the c.1318G>C (p.Gly440Arg) and c.1834A>G (p.Ser612Gly) mutations.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39283342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000297
Daniel F Ramos-Rosales, Fernando Vazquez-Alaniz, Norma Urtiz-Estrada, Eda G Ramirez-Valles, Edna M Mendez-Hernádez, Alma C Salas-Leal, Marcelo Barraza-Salas
Suicide is a complex phenomenon and a global public health problem that involves several biological factors that could contribute to the pathophysiology of suicide. There is evidence that epigenetic factors influence some psychiatric disorders, suggesting a predisposition to suicide or suicidal behavior. Here, we review studies of molecular mechanisms of suicide in an epigenetic perspective in the postmortem brain of suicide completers and peripheral blood cells of suicide attempters. Besides, we include studies of gene-specific DNA methylation, epigenome-wide association, histone modification, and interfering RNAs as epigenetic factors. This review provides an overview of the epigenetic mechanisms described in different biological systems related to suicide, contributing to an understanding of the genetic regulation in suicide. We conclude that epigenetic marks are potential biomarkers in suicide, and they could become attractive therapeutic targets due to their reversibility and importance in regulating gene expression.
{"title":"Epigenetic marks in suicide: a review.","authors":"Daniel F Ramos-Rosales, Fernando Vazquez-Alaniz, Norma Urtiz-Estrada, Eda G Ramirez-Valles, Edna M Mendez-Hernádez, Alma C Salas-Leal, Marcelo Barraza-Salas","doi":"10.1097/YPG.0000000000000297","DOIUrl":"10.1097/YPG.0000000000000297","url":null,"abstract":"<p><p>Suicide is a complex phenomenon and a global public health problem that involves several biological factors that could contribute to the pathophysiology of suicide. There is evidence that epigenetic factors influence some psychiatric disorders, suggesting a predisposition to suicide or suicidal behavior. Here, we review studies of molecular mechanisms of suicide in an epigenetic perspective in the postmortem brain of suicide completers and peripheral blood cells of suicide attempters. Besides, we include studies of gene-specific DNA methylation, epigenome-wide association, histone modification, and interfering RNAs as epigenetic factors. This review provides an overview of the epigenetic mechanisms described in different biological systems related to suicide, contributing to an understanding of the genetic regulation in suicide. We conclude that epigenetic marks are potential biomarkers in suicide, and they could become attractive therapeutic targets due to their reversibility and importance in regulating gene expression.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39326753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000282
David Curtis
Background: Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. A previous analysis of 50 000 exome-sequenced subjects failed to implicate any genes or sets of genes in which rare variants were associated with risk of affective disorder requiring specialist treatment. A much larger exome-sequenced dataset is now available.
Methods: Data from 200 632 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for 'nerves, anxiety, tension or depression'. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases.
Results: There were 22 886 cases and 176 486 controls. There were 22 642 informative genes but no gene or gene set produced a statistically significant result after correction for multiple testing. None of the genes or gene sets with the lowest P values appeared to be an obvious biological candidate.
Conclusions: The results conform exactly with the expectation under the null hypothesis. It seems unlikely that the use of common, poorly defined phenotypes will produce useful advances in understanding genetic contributions to affective disorder and it might be preferable to focus instead on obtaining large exome-sequenced samples of conditions such as bipolar 1 disorder and severe, recurrent depression. This research has been conducted using the UK Biobank Resource.
{"title":"Analysis of 200 000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of developing a mood disorder resulting in psychiatric referral.","authors":"David Curtis","doi":"10.1097/YPG.0000000000000282","DOIUrl":"10.1097/YPG.0000000000000282","url":null,"abstract":"<p><strong>Background: </strong>Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. A previous analysis of 50 000 exome-sequenced subjects failed to implicate any genes or sets of genes in which rare variants were associated with risk of affective disorder requiring specialist treatment. A much larger exome-sequenced dataset is now available.</p><p><strong>Methods: </strong>Data from 200 632 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for 'nerves, anxiety, tension or depression'. Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases.</p><p><strong>Results: </strong>There were 22 886 cases and 176 486 controls. There were 22 642 informative genes but no gene or gene set produced a statistically significant result after correction for multiple testing. None of the genes or gene sets with the lowest P values appeared to be an obvious biological candidate.</p><p><strong>Conclusions: </strong>The results conform exactly with the expectation under the null hypothesis. It seems unlikely that the use of common, poorly defined phenotypes will produce useful advances in understanding genetic contributions to affective disorder and it might be preferable to focus instead on obtaining large exome-sequenced samples of conditions such as bipolar 1 disorder and severe, recurrent depression. This research has been conducted using the UK Biobank Resource.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38960786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000292
Lin Zhang, Su Li Zhao, Zhi Hong Wang
Objective: This study summarized the clinical characteristics of X-linked adrenoleukodystrophy (X-ALD) patients in this family, and two different manifestations of the same variants in a Chinese family were reported in this article. That conducted a follow-up study to further clarify the characteristics of this disease.
Basic methods: Clinical data and test results were analyzed, and the exon region of ALD-related gene ABCD1 was sequenced by Sanger sequencing.
Main results: Gene analysis showed that there were three ABCD1 variants in the proband, c.1047C>A, c.1415-1416delAG and c.1548G>A. The elder brother of the proband had the same three variants as the proband, but showed different clinical symptoms. The mother was the carrier of three variants. Multisite variants were uncovered in this family, which caused two different manifestations of adult-onset childhood cerebral ALD and adrenomyeloneuropathy.
Principal conclusion: These findings further increase our knowledge about ABCD1 mutations and the associated phenotypes, which is beneficial for the genetic counseling of patients with X-ALD.
{"title":"Diverse clinical manifestations of X-linked adrenoleukodystrophy in a Chinese family with identical multisite variants of ABCD1 gene.","authors":"Lin Zhang, Su Li Zhao, Zhi Hong Wang","doi":"10.1097/YPG.0000000000000292","DOIUrl":"10.1097/YPG.0000000000000292","url":null,"abstract":"<p><strong>Objective: </strong>This study summarized the clinical characteristics of X-linked adrenoleukodystrophy (X-ALD) patients in this family, and two different manifestations of the same variants in a Chinese family were reported in this article. That conducted a follow-up study to further clarify the characteristics of this disease.</p><p><strong>Basic methods: </strong>Clinical data and test results were analyzed, and the exon region of ALD-related gene ABCD1 was sequenced by Sanger sequencing.</p><p><strong>Main results: </strong>Gene analysis showed that there were three ABCD1 variants in the proband, c.1047C>A, c.1415-1416delAG and c.1548G>A. The elder brother of the proband had the same three variants as the proband, but showed different clinical symptoms. The mother was the carrier of three variants. Multisite variants were uncovered in this family, which caused two different manifestations of adult-onset childhood cerebral ALD and adrenomyeloneuropathy.</p><p><strong>Principal conclusion: </strong>These findings further increase our knowledge about ABCD1 mutations and the associated phenotypes, which is beneficial for the genetic counseling of patients with X-ALD.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39283341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-01DOI: 10.1097/YPG.0000000000000293
Marco Pinna, Mirko Manchia, Claudia Pisanu, Federica Pinna, Pasquale Paribello, Andrea Carta, Anna Meloni, Claudio Conversano, Maria Del Zompo, Francesco Mola, Alessio Squassina, Bernardo Carpiniello
The effectiveness of antidepressants shows high interindividual variability ranging from full symptomatologic remission to treatment-resistant depression. Many factors can determine the variation in the clinical response, but a fundamental role is played by genetic variation within the genes encoding for the enzymes most involved in the metabolism of antidepressant drugs: the CYP2D6 and CYP2C19 isoforms of the cytochrome P450 system. This study is poised to clarify whether the different metabolizing phenotypes related to CYP2D6 and CYP2C19 could have an impact on the clinical efficacy of antidepressants and whether the frequency of these phenotypes of metabolization shows differences in the population of Sardinian patients compared to other Caucasian populations. The sample is being recruited from patients followed-up and treated at the Psychiatric Unit of the Department of Medical Science and Public Health, University of Cagliari and the University Hospital Agency of Cagliari (Italy). The study design includes three approaches: (1) a pharmacogenetic analysis of 80 patients diagnosed with MDD resistant to antidepressant treatment compared to 80 clinically responsive or remitted patients; (2) a prospective arm (N = 30) of the study where we will test the impact of genetic variation within the CYP2D6 and CYP2C19 genes on clinical response to antidepressants and on their serum levels and (3) the assessment of the socio-economic impact of antidepressant therapies, and estimation of the cost-effectiveness of the pharmacogenetic test based on CYP genes.
{"title":"Protocol for a pharmacogenetic study of antidepressants: characterization of drug-metabolizing profiles of cytochromes CYP2D6 and CYP2C19 in a Sardinian population of patients with major depressive disorder.","authors":"Marco Pinna, Mirko Manchia, Claudia Pisanu, Federica Pinna, Pasquale Paribello, Andrea Carta, Anna Meloni, Claudio Conversano, Maria Del Zompo, Francesco Mola, Alessio Squassina, Bernardo Carpiniello","doi":"10.1097/YPG.0000000000000293","DOIUrl":"10.1097/YPG.0000000000000293","url":null,"abstract":"<p><p>The effectiveness of antidepressants shows high interindividual variability ranging from full symptomatologic remission to treatment-resistant depression. Many factors can determine the variation in the clinical response, but a fundamental role is played by genetic variation within the genes encoding for the enzymes most involved in the metabolism of antidepressant drugs: the CYP2D6 and CYP2C19 isoforms of the cytochrome P450 system. This study is poised to clarify whether the different metabolizing phenotypes related to CYP2D6 and CYP2C19 could have an impact on the clinical efficacy of antidepressants and whether the frequency of these phenotypes of metabolization shows differences in the population of Sardinian patients compared to other Caucasian populations. The sample is being recruited from patients followed-up and treated at the Psychiatric Unit of the Department of Medical Science and Public Health, University of Cagliari and the University Hospital Agency of Cagliari (Italy). The study design includes three approaches: (1) a pharmacogenetic analysis of 80 patients diagnosed with MDD resistant to antidepressant treatment compared to 80 clinically responsive or remitted patients; (2) a prospective arm (N = 30) of the study where we will test the impact of genetic variation within the CYP2D6 and CYP2C19 genes on clinical response to antidepressants and on their serum levels and (3) the assessment of the socio-economic impact of antidepressant therapies, and estimation of the cost-effectiveness of the pharmacogenetic test based on CYP genes.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39201594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-08-01DOI: 10.1097/YPG.0000000000000285
Xia Wen, Xusan Xu, Xudong Luo, Jinwen Yin, Chunmei Liang, Jinyuan Zhu, Xueyan Nong, Xiudeng Zhu, Fan Ning, Shanshan Gu, Susu Xiong, Jiawu Fu, Dongjian Zhu, Zhun Dai, Dong Lv, Zhixiong Lin, Juda Lin, You Li, Guoda Ma, Yajun Wang
Nuclear casein kinase and cyclin-dependent kinase substrate 1 (nucks1) are considered a potential susceptibility gene for certain neurological diseases, such as Parkinson's disease (PD). In our study, we genotyped three single nucleotide polymorphisms (SNPs) (rs4951261, rs823114 and rs951366) of the nucks1 gene in 774 schizophrenic patients and 819 healthy controls using the improved multiplex ligation detection reaction (imLDR) technique. Furthermore, we also studied the relationship between the above SNPs and the clinical psychiatric symptoms and neurocognitive function of the patients. Genotype distributions and allele frequencies of these SNPs showed no significant differences and were found between patients and healthy controls. However, in an analysis of the positive symptom score of rs823114 among male patients, we found that the score of the A/A genotype was lower than that of the G/A+G/G genotypes (P = 0.001, P(corr) = 0.003]. Additionally, we also found that among the female patients, G allele carriers with rs823114 had lower semantic fluency scores than subjects with the A/A genotype (P = 0.010, P(corr) = 0.030]. Our data show for the first time that rs823114 polymorphism of nucks1 may affect positive symptoms and neurocognitive function in patients with schizophrenia in parts of southern China.
{"title":"Nucks1 gene polymorphism rs823114 is associated with the positive symptoms and neurocognitive function of patients with schizophrenia in parts of southern China.","authors":"Xia Wen, Xusan Xu, Xudong Luo, Jinwen Yin, Chunmei Liang, Jinyuan Zhu, Xueyan Nong, Xiudeng Zhu, Fan Ning, Shanshan Gu, Susu Xiong, Jiawu Fu, Dongjian Zhu, Zhun Dai, Dong Lv, Zhixiong Lin, Juda Lin, You Li, Guoda Ma, Yajun Wang","doi":"10.1097/YPG.0000000000000285","DOIUrl":"10.1097/YPG.0000000000000285","url":null,"abstract":"<p><p>Nuclear casein kinase and cyclin-dependent kinase substrate 1 (nucks1) are considered a potential susceptibility gene for certain neurological diseases, such as Parkinson's disease (PD). In our study, we genotyped three single nucleotide polymorphisms (SNPs) (rs4951261, rs823114 and rs951366) of the nucks1 gene in 774 schizophrenic patients and 819 healthy controls using the improved multiplex ligation detection reaction (imLDR) technique. Furthermore, we also studied the relationship between the above SNPs and the clinical psychiatric symptoms and neurocognitive function of the patients. Genotype distributions and allele frequencies of these SNPs showed no significant differences and were found between patients and healthy controls. However, in an analysis of the positive symptom score of rs823114 among male patients, we found that the score of the A/A genotype was lower than that of the G/A+G/G genotypes (P = 0.001, P(corr) = 0.003]. Additionally, we also found that among the female patients, G allele carriers with rs823114 had lower semantic fluency scores than subjects with the A/A genotype (P = 0.010, P(corr) = 0.030]. Our data show for the first time that rs823114 polymorphism of nucks1 may affect positive symptoms and neurocognitive function in patients with schizophrenia in parts of southern China.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/2d/pg-31-119.PMC8265546.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39014258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
POGZ is located on chromosome 1q21.3, encoding a pogo transposable element-derived protein with a zinc finger cluster. White-Sutton syndrome (WHSUS, OMIM:616364) is a genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ, which manifests as intellectual disability, autism spectrum disorder, specific facial features and other phenotypic spectra. To date, a total of twenty-one de novo POGZ mutations in WHSUS have been reported. Here we report the identification of a novel missense variant in the coding region of the POGZ gene (c.4042G>C), which occurred in a 15-year-old male and his mother with WHSUS. We describe their clinical features and compare them with clinical data of patients with WHSUS from the literature. Our finding broadens the spectrum of POGZ mutations and provides a good example of precision medicine through the combination of exome sequencing and clinical testing.
{"title":"A case of White-Sutton syndrome arising from a maternally-inherited mutation in POGZ.","authors":"Siqin Liu, Zhenxing Yan, Yaowei Huang, Wenxia Zheng, Yiting Deng, Yang Zou, Huifang Xie","doi":"10.1097/YPG.0000000000000288","DOIUrl":"10.1097/YPG.0000000000000288","url":null,"abstract":"<p><p>POGZ is located on chromosome 1q21.3, encoding a pogo transposable element-derived protein with a zinc finger cluster. White-Sutton syndrome (WHSUS, OMIM:616364) is a genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ, which manifests as intellectual disability, autism spectrum disorder, specific facial features and other phenotypic spectra. To date, a total of twenty-one de novo POGZ mutations in WHSUS have been reported. Here we report the identification of a novel missense variant in the coding region of the POGZ gene (c.4042G>C), which occurred in a 15-year-old male and his mother with WHSUS. We describe their clinical features and compare them with clinical data of patients with WHSUS from the literature. Our finding broadens the spectrum of POGZ mutations and provides a good example of precision medicine through the combination of exome sequencing and clinical testing.</p>","PeriodicalId":20734,"journal":{"name":"Psychiatric Genetics","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8f/47/pg-31-135.PMC8265545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39236051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}