File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Sickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients
  • Basic View
  • Metadata View
  • XML View
TitleSickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients
 
AuthorsKoenig, SC4
Becirevic, E4
Hellberg, MSC4
Li, MY4
So, JCC1
Hankins, JS3
Ware, RE3
Mcmahon, L2
Steinberg, MH2
Luo, HY4 2
Chui, DHK4 2 4
 
Issue Date2009
 
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35105
 
CitationAmerican Journal Of Hematology, 2009, v. 84 n. 9, p. 603-606 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajh.21480
 
AbstractThe β-globin gene LCR is located ∼6 kb upstream of the embryonic ε-globin gene, and is made up of five DNase I hypersensitive sites (HSs), HS 1-5. LCR plays a pivotal role in regulating the expression of downstream ε-, Gγ-, Aγ-, δ-, and β-globin genes in cis [1]. Deletions removing the LCR and parts of the downstream β-globin gene cluster in patients have been described [2]. These individuals present with a (γδβ)0-thalassemia carrier phenotype. We now report two patients with severe sickle cell disease who were compound heterozygous for Hb S mutation and novel LCR deletion. In one case, HS 1-3 were deleted; in the other, HS 1-5 were deleted. In both cases, the β-like globin genes in cis to the LCR deletions were intact. Genotypically, both patients appeared to have sickle cell trait. Coinherited with either LCR deletion, these individuals presented as sickle cell disease patients. The breakpoints of these LCR deletions were defined. These results affirm that HS 2 and 3 are primarily responsible for conferring erythroid specific high-level expression of cis-linked β-like globin genes. Furthermore, LCR deletions might cause hemolytic disease of newborns.
 
ISSN0361-8609
2012 Impact Factor: 4.003
2012 SCImago Journal Rankings: 1.101
 
DOIhttp://dx.doi.org/10.1002/ajh.21480
 
ISI Accession Number IDWOS:000269600300017
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorKoenig, SC
 
dc.contributor.authorBecirevic, E
 
dc.contributor.authorHellberg, MSC
 
dc.contributor.authorLi, MY
 
dc.contributor.authorSo, JCC
 
dc.contributor.authorHankins, JS
 
dc.contributor.authorWare, RE
 
dc.contributor.authorMcmahon, L
 
dc.contributor.authorSteinberg, MH
 
dc.contributor.authorLuo, HY
 
dc.contributor.authorChui, DHK
 
dc.date.accessioned2012-05-29T06:14:06Z
 
dc.date.available2012-05-29T06:14:06Z
 
dc.date.issued2009
 
dc.description.abstractThe β-globin gene LCR is located ∼6 kb upstream of the embryonic ε-globin gene, and is made up of five DNase I hypersensitive sites (HSs), HS 1-5. LCR plays a pivotal role in regulating the expression of downstream ε-, Gγ-, Aγ-, δ-, and β-globin genes in cis [1]. Deletions removing the LCR and parts of the downstream β-globin gene cluster in patients have been described [2]. These individuals present with a (γδβ)0-thalassemia carrier phenotype. We now report two patients with severe sickle cell disease who were compound heterozygous for Hb S mutation and novel LCR deletion. In one case, HS 1-3 were deleted; in the other, HS 1-5 were deleted. In both cases, the β-like globin genes in cis to the LCR deletions were intact. Genotypically, both patients appeared to have sickle cell trait. Coinherited with either LCR deletion, these individuals presented as sickle cell disease patients. The breakpoints of these LCR deletions were defined. These results affirm that HS 2 and 3 are primarily responsible for conferring erythroid specific high-level expression of cis-linked β-like globin genes. Furthermore, LCR deletions might cause hemolytic disease of newborns.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationAmerican Journal Of Hematology, 2009, v. 84 n. 9, p. 603-606 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ajh.21480
 
dc.identifier.citeulike6032578
 
dc.identifier.doihttp://dx.doi.org/10.1002/ajh.21480
 
dc.identifier.epage606
 
dc.identifier.isiWOS:000269600300017
 
dc.identifier.issn0361-8609
2012 Impact Factor: 4.003
2012 SCImago Journal Rankings: 1.101
 
dc.identifier.issue9
 
dc.identifier.pmid19650141
 
dc.identifier.scopuseid_2-s2.0-69549108056
 
dc.identifier.spage603
 
dc.identifier.urihttp://hdl.handle.net/10722/148611
 
dc.identifier.volume84
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35105
 
dc.publisher.placeUnited States
 
dc.relation.ispartofAmerican Journal of Hematology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdolescent
 
dc.subject.meshAnemia, Sickle Cell - Genetics
 
dc.subject.meshChild
 
dc.subject.meshFemale
 
dc.subject.meshHemoglobin, Sickle - Genetics
 
dc.subject.meshHeterozygote
 
dc.subject.meshHumans
 
dc.subject.meshMale
 
dc.subject.meshMultigene Family
 
dc.subject.meshSequence Deletion
 
dc.subject.meshBeta-Globins - Genetics
 
dc.titleSickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Koenig, SC</contributor.author>
<contributor.author>Becirevic, E</contributor.author>
<contributor.author>Hellberg, MSC</contributor.author>
<contributor.author>Li, MY</contributor.author>
<contributor.author>So, JCC</contributor.author>
<contributor.author>Hankins, JS</contributor.author>
<contributor.author>Ware, RE</contributor.author>
<contributor.author>Mcmahon, L</contributor.author>
<contributor.author>Steinberg, MH</contributor.author>
<contributor.author>Luo, HY</contributor.author>
<contributor.author>Chui, DHK</contributor.author>
<date.accessioned>2012-05-29T06:14:06Z</date.accessioned>
<date.available>2012-05-29T06:14:06Z</date.available>
<date.issued>2009</date.issued>
<identifier.citation>American Journal Of Hematology, 2009, v. 84 n. 9, p. 603-606</identifier.citation>
<identifier.issn>0361-8609</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/148611</identifier.uri>
<description.abstract>The &#946;-globin gene LCR is located &#8764;6 kb upstream of the embryonic &#949;-globin gene, and is made up of five DNase I hypersensitive sites (HSs), HS 1-5. LCR plays a pivotal role in regulating the expression of downstream &#949;-, G&#947;-, A&#947;-, &#948;-, and &#946;-globin genes in cis [1]. Deletions removing the LCR and parts of the downstream &#946;-globin gene cluster in patients have been described [2]. These individuals present with a (&#947;&#948;&#946;)0-thalassemia carrier phenotype. We now report two patients with severe sickle cell disease who were compound heterozygous for Hb S mutation and novel LCR deletion. In one case, HS 1-3 were deleted; in the other, HS 1-5 were deleted. In both cases, the &#946;-like globin genes in cis to the LCR deletions were intact. Genotypically, both patients appeared to have sickle cell trait. Coinherited with either LCR deletion, these individuals presented as sickle cell disease patients. The breakpoints of these LCR deletions were defined. These results affirm that HS 2 and 3 are primarily responsible for conferring erythroid specific high-level expression of cis-linked &#946;-like globin genes. Furthermore, LCR deletions might cause hemolytic disease of newborns.</description.abstract>
<language>eng</language>
<publisher>John Wiley &amp; Sons, Inc. The Journal&apos;s web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35105</publisher>
<relation.ispartof>American Journal of Hematology</relation.ispartof>
<subject.mesh>Adolescent</subject.mesh>
<subject.mesh>Anemia, Sickle Cell - Genetics</subject.mesh>
<subject.mesh>Child</subject.mesh>
<subject.mesh>Female</subject.mesh>
<subject.mesh>Hemoglobin, Sickle - Genetics</subject.mesh>
<subject.mesh>Heterozygote</subject.mesh>
<subject.mesh>Humans</subject.mesh>
<subject.mesh>Male</subject.mesh>
<subject.mesh>Multigene Family</subject.mesh>
<subject.mesh>Sequence Deletion</subject.mesh>
<subject.mesh>Beta-Globins - Genetics</subject.mesh>
<title>Sickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients</title>
<type>Article</type>
<description.nature>Link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1002/ajh.21480</identifier.doi>
<identifier.pmid>19650141</identifier.pmid>
<identifier.scopus>eid_2-s2.0-69549108056</identifier.scopus>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-69549108056&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>84</identifier.volume>
<identifier.issue>9</identifier.issue>
<identifier.spage>603</identifier.spage>
<identifier.epage>606</identifier.epage>
<identifier.isi>WOS:000269600300017</identifier.isi>
<publisher.place>United States</publisher.place>
<identifier.citeulike>6032578</identifier.citeulike>
</item>
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Boston University School of Medicine
  3. St. Jude Children Research Hospital
  4. Boston Medical Center