Publication: Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations
Issued Date
2006-11-01
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ISSN
14345161
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2-s2.0-33751280364
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Human Genetics. Vol.51, No.11 (2006), 1006-1014
Suggested Citation
Duangrurdee Wattanasirichaigoon, Suwat Benjaponpitak, Chonnamet Techasaensiri, Wasu Kamchaisatian, Pakit Vichyanond, Sucheela Janwityanujit, Lulin Choubtum, Sayomporn Sirinavin Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations. Journal of Human Genetics. Vol.51, No.11 (2006), 1006-1014. doi:10.1007/s10038-006-0052-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/22957
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Title
Four novel and three recurrent mutations of the BTK gene and pathogenic effects of putative splice mutations
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Abstract
X-linked agammaglobulinemia is caused by mutations in the human BTK gene, leading to recurrent pyogenic infections. We describe four novel and three known BTK-mutations in seven patients from seven (six Thai and one Burmese) families. All but one were sporadic cases. Patients 1 and 2 had recurrent mutations in exon 10 (R288W) and exon 17 (R562W), respectively. Patient 3, a previously healthy individual who presented with pseudomonas sepsis with ecthyma gangrenosum had a known mutation in exon 17 (1749delT), leading to frameshift effect (F583fsX586). Patient 4 manifested with sepsis and concurrent acute appendicitis and pneumonia. He had a mutation, IVS8 + 1G > A, which led to an insertion of intron 8 into the transcripts. In Patient 5, a novel change in exon 7, c.588G > C, initially presumed Q196H, was found to cause a leaky splicing mutation, resulting in three distinct transcripts containing 17, 108, and 190 bp of the 5′-terminal of intron 7, which led to truncated peptides consisting of 203 and 211 amino acid residues (or Q196fsX204 and Q196fsX212, respectively). Patient 6 had a mutation in exon 14 (W421X), while patient 7 had a newly defined large deletion of exons 6-9. All of the mothers tested were mutation carriers. Transcript analysis in three mothers who were heterozygous for frameshift mutations revealed a minimal amount of aberrant transcripts, while their affected children had full expression of the mutant alleles, suggesting rapid degradation due to nonsense-mediated mRNA decay in the mothers. This is the first report of mutations of BTK from Thailand. © 2006 The Japan Society of Human Genetics and Springer.