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Population differences in the polyalanine domain and 6 new mutations in HLXB9 in patients with Currarino syndrome
- Source :
- Clinical Chemistry, 52(1), 46-52. American Association for Clinical Chemistry
- Publication Year :
- 2006
-
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 (Ser185X, Trp215X, Ala26fs, Ala75fs, 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 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.
- Subjects :
- Male
Sacrum
Clinical Biochemistry
Population
Anal Canal
Biology
medicine.disease_cause
Genotype
medicine
Humans
Abnormalities, Multiple
Allele
International HapMap Project
education
Genetic association
Genetics
Homeodomain Proteins
Mutation
education.field_of_study
Polymorphism, Genetic
Biochemistry (medical)
Syndrome
medicine.disease
Pedigree
Protein Structure, Tertiary
Genetics, Population
Genetic marker
Female
Peptides
Currarino syndrome
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 00099147
- Volume :
- 52
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Clinical Chemistry
- Accession number :
- edsair.doi.dedup.....75c691921be87a1f7fb6a8025e08dcb4