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
So, MT3
Lau, DKC3
Leon, TYY3
Yuan, ZW1 3
Cai, WS1 3
Lui, VCH3
Fu, M3 5
Herbrick, JA9
Gutter, E4
Proud, V4
Li, L5
PierreLouis, J7
Aleck, K2
Van Heurn, E8
Belloni, E6
Scherer, SW9
Tam, PKH3
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
2011 Impact Factor: 7.905
2011 SCImago Journal Rankings: 0.650
DOIhttp://dx.doi.org/10.1373/clinchem.2005.056192
ISI Accession Number IDWOS:000234338800007
ReferencesReferences in Scopus
DC Field
Value
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
2011 Impact Factor: 7.905
2011 SCImago Journal Rankings: 0.650
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
Author Affiliations
  1. China Medical University Shenyang
  2. St. Joseph's Hospital and Medical Center
  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, Toronto