Does size matter? Two new deletions in the HBB gene cause β 0 -thalassemia
Most β-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to...
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Veröffentlicht in: | Annals of hematology 2022-07, Vol.101 (7), p.1465 |
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creator | Ropero, Paloma González Fernández, Fernando Ataúlfo Nieto, Jorge M Recasens, Valle Montañés, Ángeles Murúzabal, María José Sarasa, María Fernández, Cristina Villegas, Ana Benavente, Cuesta C |
description | Most β-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the β-globin gene that cause β
-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II β-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [β nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with β
-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the β-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices. |
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-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II β-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [β nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with β
-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the β-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.</description><identifier>EISSN: 1432-0584</identifier><identifier>PMID: 35467101</identifier><language>eng</language><publisher>Germany</publisher><ispartof>Annals of hematology, 2022-07, Vol.101 (7), p.1465</ispartof><rights>2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-5126-5039</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35467101$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ropero, Paloma</creatorcontrib><creatorcontrib>González Fernández, Fernando Ataúlfo</creatorcontrib><creatorcontrib>Nieto, Jorge M</creatorcontrib><creatorcontrib>Recasens, Valle</creatorcontrib><creatorcontrib>Montañés, Ángeles</creatorcontrib><creatorcontrib>Murúzabal, María José</creatorcontrib><creatorcontrib>Sarasa, María</creatorcontrib><creatorcontrib>Fernández, Cristina</creatorcontrib><creatorcontrib>Villegas, Ana</creatorcontrib><creatorcontrib>Benavente, Cuesta C</creatorcontrib><title>Does size matter? Two new deletions in the HBB gene cause β 0 -thalassemia</title><title>Annals of hematology</title><addtitle>Ann Hematol</addtitle><description>Most β-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the β-globin gene that cause β
-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II β-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [β nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with β
-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the β-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.</description><issn>1432-0584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqFzcsKgkAUgOEhiLTLK8R5AWFGx3IX2AWhrXsZ85QTziieEanH6kF6pja1bvVvPvgnzBcyCgMeJ9Jjc6I75yJMZDhjXhTLzVZw4bPzoUUC0k8Eo5zDfgf52ILFESps0OnWEmgLrkbI0hRuaBEuaiCE9ws4BK5WjSJCo9WSTa-qIVx9u2Dr0zHfZ0E3lAarouu1Uf2j-N2jv-AD6tE5Yg</recordid><startdate>202207</startdate><enddate>202207</enddate><creator>Ropero, Paloma</creator><creator>González Fernández, Fernando Ataúlfo</creator><creator>Nieto, Jorge M</creator><creator>Recasens, Valle</creator><creator>Montañés, Ángeles</creator><creator>Murúzabal, María José</creator><creator>Sarasa, María</creator><creator>Fernández, Cristina</creator><creator>Villegas, Ana</creator><creator>Benavente, Cuesta C</creator><scope>NPM</scope><orcidid>https://orcid.org/0000-0002-5126-5039</orcidid></search><sort><creationdate>202207</creationdate><title>Does size matter? Two new deletions in the HBB gene cause β 0 -thalassemia</title><author>Ropero, Paloma ; González Fernández, Fernando Ataúlfo ; Nieto, Jorge M ; Recasens, Valle ; Montañés, Ángeles ; Murúzabal, María José ; Sarasa, María ; Fernández, Cristina ; Villegas, Ana ; Benavente, Cuesta C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_354671013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ropero, Paloma</creatorcontrib><creatorcontrib>González Fernández, Fernando Ataúlfo</creatorcontrib><creatorcontrib>Nieto, Jorge M</creatorcontrib><creatorcontrib>Recasens, Valle</creatorcontrib><creatorcontrib>Montañés, Ángeles</creatorcontrib><creatorcontrib>Murúzabal, María José</creatorcontrib><creatorcontrib>Sarasa, María</creatorcontrib><creatorcontrib>Fernández, Cristina</creatorcontrib><creatorcontrib>Villegas, Ana</creatorcontrib><creatorcontrib>Benavente, Cuesta C</creatorcontrib><collection>PubMed</collection><jtitle>Annals of hematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ropero, Paloma</au><au>González Fernández, Fernando Ataúlfo</au><au>Nieto, Jorge M</au><au>Recasens, Valle</au><au>Montañés, Ángeles</au><au>Murúzabal, María José</au><au>Sarasa, María</au><au>Fernández, Cristina</au><au>Villegas, Ana</au><au>Benavente, Cuesta C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Does size matter? Two new deletions in the HBB gene cause β 0 -thalassemia</atitle><jtitle>Annals of hematology</jtitle><addtitle>Ann Hematol</addtitle><date>2022-07</date><risdate>2022</risdate><volume>101</volume><issue>7</issue><spage>1465</spage><pages>1465-</pages><eissn>1432-0584</eissn><abstract>Most β-thalassemias are caused by mutations involving one or a limited number of nucleotides within the gene or its adjacent regions. They can be substitutions or deletions; in these cases, the loss ranges from a single nucleotide to even the entire HBB gene, so we wonder if the phenotype is due to the size of the deletion or the location of the mutation. To clarify this, we present two new deletions in the β-globin gene that cause β
-thalassemia. The hematological parameters were determined with an automated cell counter; the Hb A2 and Hb F levels were measured by performance liquid chromatography. Hemoglobins were analyzed by capillary zone electrophoresis (Sebia Capillarys Flex system) and ion-exchange HPLC (BioRad Variant II β-thalassemia Short Program). Molecular characterization was performed by automatic Sanger sequencing. The screening of common α-thalassemia point mutations and deletions in the world (21 in total) were carried out using multiplex PCR followed by reverse-hybridization with a commercial Alpha-Globin StripAssay kit. We have characterized two new mutations-(1) 1-bp deletion [CD61/62(-G)] [HBB:c.186_187delG], (2) 105-bp deletion [IVS-2-nt767-CD111] [HBB:c.316-84_333del]-and we have described, for first time in Spain, the 25-bp deletion [β nts 252 - 276 deleted] [HBB:c.93-22_95del] mutation. These mutations were classified as pathogenic by UniProt Variants confirmed according to the American College of Medical Genetics and Genomics guidelines. These mutations present a phenotype compatible with β
-thalassemia, supported by hematological parameters that correlate the degree of reduction in the synthesis of the β-globin chain. Identification of this type of mutation is important for genetic counselling of partners where both are carriers, so that they are aware of the genetic risk of having affected children, allowing them to take an informed decision about their reproductive choices.</abstract><cop>Germany</cop><pmid>35467101</pmid><orcidid>https://orcid.org/0000-0002-5126-5039</orcidid></addata></record> |
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title | Does size matter? Two new deletions in the HBB gene cause β 0 -thalassemia |
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