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Article: Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome
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TitlePopulation differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome
 
AuthorsGarciaBarceló, M3 3
So, MT3 3
Lau, DKC3
Leon, TYY3
Yuan, ZW3 2
Cai, WS3 2
Lui, VCH3
Fu, M3 5
Herbrick, JA9
Gutter, E4
Proud, V4
Li, L5
PierreLouis, J7
Aleck, K1
Van Heurn, E8
Belloni, E6
Scherer, SW9
Tam, PKH3 3 3
 
Issue Date2006
 
PublisherAmerican Association for Clinical Chemistry, Inc. The Journal's web site is located at http://www.clinchem.org
 
CitationClinical Chemistry, 2006, v. 52 n. 1, p. 46-52 [How to Cite?]
DOI: http://dx.doi.org/10.1373/clinchem.2005.056192
 
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.
 
ISSN0009-9147
2012 Impact Factor: 7.149
2012 SCImago Journal Rankings: 2.093
 
DOIhttp://dx.doi.org/10.1373/clinchem.2005.056192
 
ISI Accession Number IDWOS:000234338800007
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorGarciaBarceló, M
 
dc.contributor.authorSo, MT
 
dc.contributor.authorLau, DKC
 
dc.contributor.authorLeon, TYY
 
dc.contributor.authorYuan, ZW
 
dc.contributor.authorCai, WS
 
dc.contributor.authorLui, VCH
 
dc.contributor.authorFu, M
 
dc.contributor.authorHerbrick, JA
 
dc.contributor.authorGutter, E
 
dc.contributor.authorProud, V
 
dc.contributor.authorLi, L
 
dc.contributor.authorPierreLouis, J
 
dc.contributor.authorAleck, K
 
dc.contributor.authorVan Heurn, E
 
dc.contributor.authorBelloni, E
 
dc.contributor.authorScherer, SW
 
dc.contributor.authorTam, PKH
 
dc.date.accessioned2010-09-06T08:40:28Z
 
dc.date.available2010-09-06T08:40:28Z
 
dc.date.issued2006
 
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.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationClinical Chemistry, 2006, v. 52 n. 1, p. 46-52 [How to Cite?]
DOI: http://dx.doi.org/10.1373/clinchem.2005.056192
 
dc.identifier.doihttp://dx.doi.org/10.1373/clinchem.2005.056192
 
dc.identifier.epage52
 
dc.identifier.hkuros112900
 
dc.identifier.isiWOS:000234338800007
 
dc.identifier.issn0009-9147
2012 Impact Factor: 7.149
2012 SCImago Journal Rankings: 2.093
 
dc.identifier.issue1
 
dc.identifier.openurl
 
dc.identifier.pmid16254195
 
dc.identifier.scopuseid_2-s2.0-29744438814
 
dc.identifier.spage46
 
dc.identifier.urihttp://hdl.handle.net/10722/83391
 
dc.identifier.volume52
 
dc.languageeng
 
dc.publisherAmerican Association for Clinical Chemistry, Inc. The Journal's web site is located at http://www.clinchem.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofClinical Chemistry
 
dc.relation.referencesReferences in Scopus
 
dc.titlePopulation differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome
 
dc.typeArticle
 
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<contributor.author>Cai, WS</contributor.author>
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<description.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 &lt;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. &#169; 2006 American Association for Clinical Chemistry.</description.abstract>
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Author Affiliations
  1. St. Joseph's Hospital and Medical Center
  2. China Medical University Shenyang
  3. The University of Hong Kong
  4. Children's Hospital of The King's Daughters Health System
  5. Beijing Children's Hospital
  6. Istituto Europeo di Oncologia
  7. University of Toronto
  8. University Hospital Maastricht
  9. Hospital for Sick Children University of Toronto