Differences in methylation patterns in the methylation boundary region of IDS gene in Hunter syndrome patients: implications for CpG hot spot mutations

European Journal of Human Genetics : EJHG
Shunji TomatsuWilliam S Sly

Abstract

Hunter syndrome, an X-linked disorder, results from deficiency of iduronate-2-sulfatase (IDS). Around 40% of independent point mutations at IDS were found at CpG sites as transitional events. The 15 CpG sites in the coding sequences of exons 1 and 2, which are normally hypomethylated, account for very few of transitional mutations. By contrast, the CpG sites in the coding sequences of exon 3, though also normally hypomethylated, account for much higher fraction of transitional mutations. To better understand relationship between methylation status and CpG transitional mutations in this region, the methylation patterns of 11 Hunter patients with transitional mutations at CpG sites were investigated using bisulfite genomic sequencing. The patient cohort mutation spectrum is composed of one mutation in exon 1 (one patient) and three different mutations in exon 3 (10 patients). We confirmed that in normal males, cytosines at the CpG sites from the promoter region to a portion of intron 3 were hypomethylated. However, specific CpG sites in this area were more highly methylated in patients. The patients with p.R8X (exon 1), p.P86L (exon 3), and p.R88H (exon 3) mutations had a hypermethylated condition in exon 2 to intron 3 but retain...Continue Reading

References

Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P J WilsonJ J Hopwood
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S KochanekW Doerfler
Feb 1, 1988·Human Genetics·D N Cooper, H Youssoufian
Jul 20, 1987·Journal of Molecular Biology·M Gardiner-Garden, M Frommer
Apr 1, 1995·Current Opinion in Genetics & Development·R A Martienssen, E J Richards
Aug 11, 1994·Nucleic Acids Research·S J ClarkM Frommer
Sep 1, 1993·Genomics·P J WilsonC P Morris
Jan 1, 1996·Human Mutation·S L GoldenfumB Winchester
Oct 8, 1998·Journal of Inherited Metabolic Disease·L GortM J Coll
Jan 6, 1999·Archives of Disease in Childhood·E VafiadakiJ E Wraith
Jun 6, 2000·Biochimica Et Biophysica Acta·G R VillaniP Di Natale
May 20, 2003·Human Mutation·Peter D StensonDavid N Cooper
Jul 6, 2004·Journal of Medical Genetics·S TomatsuA Noguchi

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Citations

Oct 21, 2011·Biochemistry Research International·Maria Francisca CoutinhoSandra Alves
Oct 16, 2013·Molecular Genetics and Metabolism·A C Brusius-FacchinS Leistner-Segal
Aug 7, 2019·The FEBS Journal·Sepideh MikaeeliNabil G Seidah
Sep 18, 2017·Molecular Genetics and Metabolism·Shahzeb HassanNahid Tayebi

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