A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis

Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Maria d’Apolito [verfasserIn] Caterina Ceccarini [verfasserIn] Rosa Savino [verfasserIn] Iolanda Adipietro [verfasserIn] Ighli di Bari [verfasserIn] Rosa Santacroce [verfasserIn] Maria Curcetti [verfasserIn] Giovanna D’Andrea [verfasserIn] Anna-Irma Croce [verfasserIn] Carla Cesarano [verfasserIn] Anna Nunzia Polito [verfasserIn] Maurizio Margaglione [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	gene SK2 channel developmental delay essential tremor

Übergeordnetes Werk:	In: Genes - MDPI AG, 2010, 14(2023), 7, p 1380
Übergeordnetes Werk:	volume:14 ; year:2023 ; number:7, p 1380

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/genes14071380

Katalog-ID:	DOAJ093898622

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allfields	10.3390/genes14071380 doi (DE-627)DOAJ093898622 (DE-599)DOAJca3cee81ab2f42f2862aecee71f64c56 DE-627 ger DE-627 rakwb eng QH426-470 Maria d’Apolito verfasserin aut A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. gene <i<KCNN2</i< SK2 channel developmental delay essential tremor Genetics Caterina Ceccarini verfasserin aut Rosa Savino verfasserin aut Iolanda Adipietro verfasserin aut Ighli di Bari verfasserin aut Rosa Santacroce verfasserin aut Maria Curcetti verfasserin aut Giovanna D’Andrea verfasserin aut Anna-Irma Croce verfasserin aut Carla Cesarano verfasserin aut Anna Nunzia Polito verfasserin aut Maurizio Margaglione verfasserin aut In Genes MDPI AG, 2010 14(2023), 7, p 1380 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:7, p 1380 https://doi.org/10.3390/genes14071380 kostenfrei https://doaj.org/article/ca3cee81ab2f42f2862aecee71f64c56 kostenfrei https://www.mdpi.com/2073-4425/14/7/1380 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 7, p 1380
spelling	10.3390/genes14071380 doi (DE-627)DOAJ093898622 (DE-599)DOAJca3cee81ab2f42f2862aecee71f64c56 DE-627 ger DE-627 rakwb eng QH426-470 Maria d’Apolito verfasserin aut A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. gene <i<KCNN2</i< SK2 channel developmental delay essential tremor Genetics Caterina Ceccarini verfasserin aut Rosa Savino verfasserin aut Iolanda Adipietro verfasserin aut Ighli di Bari verfasserin aut Rosa Santacroce verfasserin aut Maria Curcetti verfasserin aut Giovanna D’Andrea verfasserin aut Anna-Irma Croce verfasserin aut Carla Cesarano verfasserin aut Anna Nunzia Polito verfasserin aut Maurizio Margaglione verfasserin aut In Genes MDPI AG, 2010 14(2023), 7, p 1380 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:7, p 1380 https://doi.org/10.3390/genes14071380 kostenfrei https://doaj.org/article/ca3cee81ab2f42f2862aecee71f64c56 kostenfrei https://www.mdpi.com/2073-4425/14/7/1380 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 7, p 1380
allfields_unstemmed	10.3390/genes14071380 doi (DE-627)DOAJ093898622 (DE-599)DOAJca3cee81ab2f42f2862aecee71f64c56 DE-627 ger DE-627 rakwb eng QH426-470 Maria d’Apolito verfasserin aut A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. gene <i<KCNN2</i< SK2 channel developmental delay essential tremor Genetics Caterina Ceccarini verfasserin aut Rosa Savino verfasserin aut Iolanda Adipietro verfasserin aut Ighli di Bari verfasserin aut Rosa Santacroce verfasserin aut Maria Curcetti verfasserin aut Giovanna D’Andrea verfasserin aut Anna-Irma Croce verfasserin aut Carla Cesarano verfasserin aut Anna Nunzia Polito verfasserin aut Maurizio Margaglione verfasserin aut In Genes MDPI AG, 2010 14(2023), 7, p 1380 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:7, p 1380 https://doi.org/10.3390/genes14071380 kostenfrei https://doaj.org/article/ca3cee81ab2f42f2862aecee71f64c56 kostenfrei https://www.mdpi.com/2073-4425/14/7/1380 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 7, p 1380
allfieldsGer	10.3390/genes14071380 doi (DE-627)DOAJ093898622 (DE-599)DOAJca3cee81ab2f42f2862aecee71f64c56 DE-627 ger DE-627 rakwb eng QH426-470 Maria d’Apolito verfasserin aut A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. gene <i<KCNN2</i< SK2 channel developmental delay essential tremor Genetics Caterina Ceccarini verfasserin aut Rosa Savino verfasserin aut Iolanda Adipietro verfasserin aut Ighli di Bari verfasserin aut Rosa Santacroce verfasserin aut Maria Curcetti verfasserin aut Giovanna D’Andrea verfasserin aut Anna-Irma Croce verfasserin aut Carla Cesarano verfasserin aut Anna Nunzia Polito verfasserin aut Maurizio Margaglione verfasserin aut In Genes MDPI AG, 2010 14(2023), 7, p 1380 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:7, p 1380 https://doi.org/10.3390/genes14071380 kostenfrei https://doaj.org/article/ca3cee81ab2f42f2862aecee71f64c56 kostenfrei https://www.mdpi.com/2073-4425/14/7/1380 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 7, p 1380
allfieldsSound	10.3390/genes14071380 doi (DE-627)DOAJ093898622 (DE-599)DOAJca3cee81ab2f42f2862aecee71f64c56 DE-627 ger DE-627 rakwb eng QH426-470 Maria d’Apolito verfasserin aut A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium. gene <i<KCNN2</i< SK2 channel developmental delay essential tremor Genetics Caterina Ceccarini verfasserin aut Rosa Savino verfasserin aut Iolanda Adipietro verfasserin aut Ighli di Bari verfasserin aut Rosa Santacroce verfasserin aut Maria Curcetti verfasserin aut Giovanna D’Andrea verfasserin aut Anna-Irma Croce verfasserin aut Carla Cesarano verfasserin aut Anna Nunzia Polito verfasserin aut Maurizio Margaglione verfasserin aut In Genes MDPI AG, 2010 14(2023), 7, p 1380 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:7, p 1380 https://doi.org/10.3390/genes14071380 kostenfrei https://doaj.org/article/ca3cee81ab2f42f2862aecee71f64c56 kostenfrei https://www.mdpi.com/2073-4425/14/7/1380 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 7, p 1380
language	English
source	In Genes 14(2023), 7, p 1380 volume:14 year:2023 number:7, p 1380
sourceStr	In Genes 14(2023), 7, p 1380 volume:14 year:2023 number:7, p 1380
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	gene <i<KCNN2</i< SK2 channel developmental delay essential tremor Genetics
isfreeaccess_bool	true
container_title	Genes
authorswithroles_txt_mv	Maria d’Apolito @@aut@@ Caterina Ceccarini @@aut@@ Rosa Savino @@aut@@ Iolanda Adipietro @@aut@@ Ighli di Bari @@aut@@ Rosa Santacroce @@aut@@ Maria Curcetti @@aut@@ Giovanna D’Andrea @@aut@@ Anna-Irma Croce @@aut@@ Carla Cesarano @@aut@@ Anna Nunzia Polito @@aut@@ Maurizio Margaglione @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	614096537
id	DOAJ093898622
language_de	englisch
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Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. 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callnumber-first	Q - Science
author	Maria d’Apolito
spellingShingle	Maria d’Apolito misc QH426-470 misc gene misc <i<KCNN2</i< misc SK2 channel misc developmental delay misc essential tremor misc Genetics A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis
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topic_title	QH426-470 A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis gene <i<KCNN2</i< SK2 channel developmental delay essential tremor
topic	misc QH426-470 misc gene misc <i<KCNN2</i< misc SK2 channel misc developmental delay misc essential tremor misc Genetics
topic_unstemmed	misc QH426-470 misc gene misc <i<KCNN2</i< misc SK2 channel misc developmental delay misc essential tremor misc Genetics
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title	A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis
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title_full	A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis
author_sort	Maria d’Apolito
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author_browse	Maria d’Apolito Caterina Ceccarini Rosa Savino Iolanda Adipietro Ighli di Bari Rosa Santacroce Maria Curcetti Giovanna D’Andrea Anna-Irma Croce Carla Cesarano Anna Nunzia Polito Maurizio Margaglione
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title_sort	novel <i<kcnn2</i< variant in a family with essential tremor plus: clinical characteristics and in silico analysis
callnumber	QH426-470
title_auth	A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis
abstract	Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium.
abstractGer	Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium.
abstract_unstemmed	Background: Essential tremor (ET) is one of the more common movement disorders. Current diagnosis is solely based on clinical findings. ET appears to be inherited in an autosomal dominant pattern. Several loci on specific chromosomes have been studied by linkage analysis, but the causes of essential tremor are still unknown in many patients. Genetic studies described the association of several genes with familial ET. However, they were found only in distinct families, suggesting that some can be private pathogenic variants. Aim of the Study: to characterize the phenotype of an Italian family with ET and identify the genetic variant associated. Methods: Clinical and genetic examinations were performed. Genetic testing was done with whole-exome sequencing (WES) using the Illumina platform. Bidirectional capillary Sanger sequencing was used to investigate the presence of variant in all affected members of the family. In silico prediction of pathogenicity was used to study the effect of gene variants on protein structure. Results: The proband was a 15-year-old boy. The patient was the first of two children of a non-consanguineous couple. Family history was remarkable for tremor in the mother line. His mother suffered from bilateral upper extremity kinetic tremors (since she was 20 years old), anxiety, and depression. Other relatives referred bilateral upper extremity tremors. In the index case, WES analysis performed supposing a dominant mode of inheritance, identified a novel heterozygous missense variant in potassium calcium-activated channel subfamily N member 2 (<i<KCNN2</i<) (NM_021614.3: c.1145G<A, p.Gly382Asp). In the pedigree investigation, all carriers of the gene variant had ET and showed variable expressivity, the elder symptomatic relative showing cognitive impairment and hallucinations in the last decade, in addition to tremor since a young age. The amino acid residue #382 is located in a transmembrane region and in silico analysis suggested a causative role for the variant. Modelling of the mutant protein structure showed that the variant causes a clash in the protein structure. Therefore, the variant could cause a conformational change that alters the ability of the protein in the modulation of ion channels Conclusions: The <i<KCNN2</i< gene variant identified could be associated with ET. The variant could modify a voltage-independent potassium channel activated by intracellular calcium.
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title_short	A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis
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author2	Caterina Ceccarini Rosa Savino Iolanda Adipietro Ighli di Bari Rosa Santacroce Maria Curcetti Giovanna D’Andrea Anna-Irma Croce Carla Cesarano Anna Nunzia Polito Maurizio Margaglione
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A Novel <i<KCNN2</i< Variant in a Family with Essential Tremor Plus: Clinical Characteristics and In Silico Analysis

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