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Article: Genetic predisposition of white matter infarction with protein S deficiency and R355C mutation

TitleGenetic predisposition of white matter infarction with protein S deficiency and R355C mutation
Authors
Issue Date2010
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurology.org
Citation
Neurology, 2010, v. 75 n. 24, p. 2185-2189 How to Cite?
AbstractBackground: The association between protein S deficiency (PSD) and ischemic stroke is controversial and warrants further investigation. Methods: We conducted a genotype and MRI correlation study in a Chinese family in which hereditary PSD cosegregated with premature ischemic strokes. Six out of 11 family members inherited PSD type III in an autosomal dominant manner. Results: Among all PSD members, a novel missense mutation 1063C→T in exon 10 of protein S alpha (PROS1) was identified, which encoded a substitution of arginine to cysteine at position 355 (R355C) in the first globular domain of laminin A of protein S. Wild-type PROS1 sequences were retained in non-PSD members. MRI detected deep white matter infarctions predominantly distributed in the borderzone regions. The infarct topography was homogeneous in all adult mutant carriers. By contrast, cerebral infarction was absent in nonmutant carriers. Extensive investigation in the family did not reveal any confounding stroke risk. Haplotype analysis with high-density single nucleotide polymorphism markers revealed a 6.1-Mb minimally rearranged region (rs12494685 to rs1598240) in 3q11.2, lod = 3.0. Among the 7 annotated genes in this region, PROS1 is known to be associated with thrombotic disorders. MRI screening in an additional 10 PSD families without R355C showed no cerebral infarction. Conclusions: PROS1 R355C mutation cosegregated with PSD type III and premature white matter infarctions in the index family. The findings substantiate an association between PSD and stroke. Study of the mechanism underlying this association may improve our understanding of premature cryptogenic white matter infarction. © 2010 by AAN Enterprises, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/139930
ISSN
2015 Impact Factor: 8.166
2015 SCImago Journal Rankings: 3.691
ISI Accession Number ID
Funding AgencyGrant Number
S.H. Ho Foundation
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong
Funding Information:

Study funding: Supported by S.H. Ho Foundation and Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorLeung, TWen_HK
dc.contributor.authorYip, SFen_HK
dc.contributor.authorLam, CWen_HK
dc.contributor.authorChan, TLen_HK
dc.contributor.authorLam, WWMen_HK
dc.contributor.authorSiu, DYWen_HK
dc.contributor.authorFan, YHen_HK
dc.contributor.authorChan, NPHen_HK
dc.contributor.authorLiu, HSYen_HK
dc.contributor.authorChan, LCen_HK
dc.contributor.authorWong, KSen_HK
dc.date.accessioned2011-09-23T06:01:46Z-
dc.date.available2011-09-23T06:01:46Z-
dc.date.issued2010en_HK
dc.identifier.citationNeurology, 2010, v. 75 n. 24, p. 2185-2189en_HK
dc.identifier.issn0028-3878en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139930-
dc.description.abstractBackground: The association between protein S deficiency (PSD) and ischemic stroke is controversial and warrants further investigation. Methods: We conducted a genotype and MRI correlation study in a Chinese family in which hereditary PSD cosegregated with premature ischemic strokes. Six out of 11 family members inherited PSD type III in an autosomal dominant manner. Results: Among all PSD members, a novel missense mutation 1063C→T in exon 10 of protein S alpha (PROS1) was identified, which encoded a substitution of arginine to cysteine at position 355 (R355C) in the first globular domain of laminin A of protein S. Wild-type PROS1 sequences were retained in non-PSD members. MRI detected deep white matter infarctions predominantly distributed in the borderzone regions. The infarct topography was homogeneous in all adult mutant carriers. By contrast, cerebral infarction was absent in nonmutant carriers. Extensive investigation in the family did not reveal any confounding stroke risk. Haplotype analysis with high-density single nucleotide polymorphism markers revealed a 6.1-Mb minimally rearranged region (rs12494685 to rs1598240) in 3q11.2, lod = 3.0. Among the 7 annotated genes in this region, PROS1 is known to be associated with thrombotic disorders. MRI screening in an additional 10 PSD families without R355C showed no cerebral infarction. Conclusions: PROS1 R355C mutation cosegregated with PSD type III and premature white matter infarctions in the index family. The findings substantiate an association between PSD and stroke. Study of the mechanism underlying this association may improve our understanding of premature cryptogenic white matter infarction. © 2010 by AAN Enterprises, Inc.en_HK
dc.languageengen_US
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.neurology.orgen_HK
dc.relation.ispartofNeurologyen_HK
dc.subject.meshBrain - blood supply - pathology-
dc.subject.meshCerebral Infarction - genetics - pathology-
dc.subject.meshMutation, Missense-
dc.subject.meshProtein S - genetics-
dc.subject.meshProtein S Deficiency - complications-
dc.titleGenetic predisposition of white matter infarction with protein S deficiency and R355C mutationen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0028-3878&volume=75&issue=24&spage=2185&epage=2189&date=2010&atitle=Genetic+predisposition+of+white+matter+infarction+with+protein+S+deficiency+and+R355C+mutation-
dc.identifier.emailLam, CW:ching-wanlam@pathology.hku.hken_HK
dc.identifier.authorityLam, CW=rp00260en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1212/WNL.0b013e3182020379en_HK
dc.identifier.pmid21172841-
dc.identifier.scopuseid_2-s2.0-78650852015en_HK
dc.identifier.hkuros192467en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650852015&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume75en_HK
dc.identifier.issue24en_HK
dc.identifier.spage2185en_HK
dc.identifier.epage2189en_HK
dc.identifier.eissn1526-632X-
dc.identifier.isiWOS:000285292700011-
dc.publisher.placeUnited Statesen_HK

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