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Article: Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome

TitlePopulation differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome
Authors
Issue Date2006
PublisherAmerican Association for Clinical Chemistry, Inc. The Journal's web site is located at http://www.clinchem.org
Citation
Clinical Chemistry, 2006, v. 52 n. 1, p. 46-52 How to Cite?
Abstract
Background: The combination of partial absence of the sacrum, anorectal anomalies, and presacral mass constitutes Currarino syndrome (CS), which is associated with mutations in HLXB9. Methods: We analyzed 5 CS families and 6 sporadic cases for HLXB9 mutations by direct sequencing. Potentially pathologic expansions of HLXB9 GCC repeats were analyzed in patients, 4 general populations [Chinese, Japanese, Yoruba, and Centre du Etude Polymorphisme Human (CEPH)] from the HapMap project, and 145 healthy Chinese. Results: We identified 6 novel mutations affecting highly conserved residues (Serl85X, Trp215X, Ala26fs, Ala75/s, Met1Ile, and Arg273Cys). GCC allele and genotype distributions showed marked statistically significant differences. (GCC) 11 was the most common allele overall; its frequency ranged from 90% in CEPH to 68% in Yoruba and 50% in Chinese and Japanese populations. (GCC) 9 was almost as common as (GCC) 11 in Chinese and Japanese populations, whereas its frequency was <10% in Yoruba and CEPH populations. The Yoruba population had the highest frequency of the largest alleles [(GCC) 12 and (GCC) 13], which were almost absent in the other groups. Conclusions: Lack of HLXB9 mutations in some patients and the presence of variable phenotypes suggest DNA alterations in HLXB9 noncoding regions and/or in other genes encoding HLXB9 regulatory molecules or protein partners. If HLXB9, like other homeobox genes, has a threshold beyond which triplet expansions are pathologic, those populations enriched with larger alleles would be at a higher risk. The data illustrate the importance of ethnicity adjustment if these polymorphic markers are to be used in association studies. © 2006 American Association for Clinical Chemistry.
Persistent Identifierhttp://hdl.handle.net/10722/83391
ISSN
2013 Impact Factor: 7.768
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGarciaBarceló, Men_HK
dc.contributor.authorSo, MTen_HK
dc.contributor.authorLau, DKCen_HK
dc.contributor.authorLeon, TYYen_HK
dc.contributor.authorYuan, ZWen_HK
dc.contributor.authorCai, WSen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorFu, Men_HK
dc.contributor.authorHerbrick, JAen_HK
dc.contributor.authorGutter, Een_HK
dc.contributor.authorProud, Ven_HK
dc.contributor.authorLi, Len_HK
dc.contributor.authorPierreLouis, Jen_HK
dc.contributor.authorAleck, Ken_HK
dc.contributor.authorVan Heurn, Een_HK
dc.contributor.authorBelloni, Een_HK
dc.contributor.authorScherer, SWen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T08:40:28Z-
dc.date.available2010-09-06T08:40:28Z-
dc.date.issued2006en_HK
dc.identifier.citationClinical Chemistry, 2006, v. 52 n. 1, p. 46-52en_HK
dc.identifier.issn0009-9147en_HK
dc.identifier.urihttp://hdl.handle.net/10722/83391-
dc.description.abstractBackground: The combination of partial absence of the sacrum, anorectal anomalies, and presacral mass constitutes Currarino syndrome (CS), which is associated with mutations in HLXB9. Methods: We analyzed 5 CS families and 6 sporadic cases for HLXB9 mutations by direct sequencing. Potentially pathologic expansions of HLXB9 GCC repeats were analyzed in patients, 4 general populations [Chinese, Japanese, Yoruba, and Centre du Etude Polymorphisme Human (CEPH)] from the HapMap project, and 145 healthy Chinese. Results: We identified 6 novel mutations affecting highly conserved residues (Serl85X, Trp215X, Ala26fs, Ala75/s, Met1Ile, and Arg273Cys). GCC allele and genotype distributions showed marked statistically significant differences. (GCC) 11 was the most common allele overall; its frequency ranged from 90% in CEPH to 68% in Yoruba and 50% in Chinese and Japanese populations. (GCC) 9 was almost as common as (GCC) 11 in Chinese and Japanese populations, whereas its frequency was <10% in Yoruba and CEPH populations. The Yoruba population had the highest frequency of the largest alleles [(GCC) 12 and (GCC) 13], which were almost absent in the other groups. Conclusions: Lack of HLXB9 mutations in some patients and the presence of variable phenotypes suggest DNA alterations in HLXB9 noncoding regions and/or in other genes encoding HLXB9 regulatory molecules or protein partners. If HLXB9, like other homeobox genes, has a threshold beyond which triplet expansions are pathologic, those populations enriched with larger alleles would be at a higher risk. The data illustrate the importance of ethnicity adjustment if these polymorphic markers are to be used in association studies. © 2006 American Association for Clinical Chemistry.en_HK
dc.languageengen_HK
dc.publisherAmerican Association for Clinical Chemistry, Inc. The Journal's web site is located at http://www.clinchem.orgen_HK
dc.relation.ispartofClinical Chemistryen_HK
dc.titlePopulation differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndromeen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0009-9147&volume=52&issue=1&spage=46&epage=52&date=2006&atitle=Population+differences+in+the+polyalanine+domain+and+6+new+mutations+in+HLXB9+in+patients+with+Currarino+syndromeen_HK
dc.identifier.emailGarciaBarceló, M: mmgarcia@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.authorityGarciaBarceló, M=rp00445en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1373/clinchem.2005.056192en_HK
dc.identifier.pmid16254195en_HK
dc.identifier.scopuseid_2-s2.0-29744438814en_HK
dc.identifier.hkuros112900en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-29744438814&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume52en_HK
dc.identifier.issue1en_HK
dc.identifier.spage46en_HK
dc.identifier.epage52en_HK
dc.identifier.isiWOS:000234338800007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridGarciaBarceló, M=6701767303en_HK
dc.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridLau, DKC=10642145100en_HK
dc.identifier.scopusauthoridLeon, TYY=10641704600en_HK
dc.identifier.scopusauthoridYuan, ZW=10641253300en_HK
dc.identifier.scopusauthoridCai, WS=10640261800en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridFu, M=49761323800en_HK
dc.identifier.scopusauthoridHerbrick, JA=6602297751en_HK
dc.identifier.scopusauthoridGutter, E=10641452500en_HK
dc.identifier.scopusauthoridProud, V=6603667932en_HK
dc.identifier.scopusauthoridLi, L=7501448457en_HK
dc.identifier.scopusauthoridPierreLouis, J=14067555600en_HK
dc.identifier.scopusauthoridAleck, K=6601930107en_HK
dc.identifier.scopusauthoridVan Heurn, E=16041024000en_HK
dc.identifier.scopusauthoridBelloni, E=7003332359en_HK
dc.identifier.scopusauthoridScherer, SW=35374654500en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK

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