Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome.

Human Mutation
Susanna LualdiM Filocamo

Abstract

Sequence analysis of the X-linked iduronate-2-sulfatase (IDS) gene in two Hunter syndrome patients revealed a lack of concordance between IDS genomic DNA and cDNA. These individuals were found to be hemizygous respectively for a nonsense mutation [c.22C>T;p.R8X] and a frameshift micro-insertion [c.10insT;p.P4Sfs] in their genomic DNA. However, both wild-type and mutant IDS sequences were evident upon cDNA analysis. Similar discrepant results were also obtained in a third unrelated patient carrying the same p.R8X mutation. Since both p.R8X mutations were inherited from carrier mothers, somatic mosaicism could be excluded. Although the presence of wild-type IDSmRNA-transcripts was confirmed in all three patients by restriction enzyme digestion, clone sequencing, pyrosequencing and single nucleotide primer extension (SNuPE), no wild-type IDS genomic sequence was detectable. The relative abundance of wild-type and mutation-bearing IDS-transcripts in different tissues was quantified by SNuPE. Although IDS transcript levels, as measured by real-time PCR, were reduced (51-71% normal) in these patients, some wild-type IDS protein was detectable by western blotting. Various possible explanations for these unprecedented findings (e.g. ac...Continue Reading

Citations

Apr 21, 2011·Human Genomics·Mirella Filocamo, Amelia Morrone
Feb 20, 2020·International Journal of Molecular Sciences·Francesca D'AvanzoRosella Tomanin
Nov 20, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Cheng ZhangChengchao Shou
Nov 18, 2018·Italian Journal of Pediatrics·Mirella FilocamoAmelia Morrone

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