Article: Sickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients

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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, HY2 4
Chui, DHK2 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
2011 Impact Factor: 4.671
2011 SCImago Journal Rankings: 0.308
DOIhttp://dx.doi.org/10.1002/ajh.21480
ISI Accession Number IDWOS:000269600300017
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 4.671
2011 SCImago Journal Rankings: 0.308
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
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