Two other IDUA mutations occurred in CpG dinucleotides (678 G→A and Y202X) and were found in the same patient, along with M133I. The analysis of parental DNA showed that the mutation M133I was linked to the Y202X mutation in the father whereas the other mutation (678 G→A) was maternally inherited. The 678 G→A mutation, a transition in the first base of intron 6, is also a splice site mutation that would cause the change of a glycine to an aspartic acid in position 196 of the protein. However, since skin fibroblasts from this patient were not available, it was not known whether mutant mRNA coding for the G197D α-l-iduronidase was produced. Therefore, this IDUA change was considered only as a splice mutation and was not expressed in CHO-K1 cells.
Case#: Patient #19, Brazilian
DiseaseAssertion: MPS1, severe(Hurler)
FamilyInfo: n/a
CasePresentingHPOs:
CaseHPOFreeText: underwent bone marrow transplant
CaseNotHPOs:
CaseNotHPOFreeText:
Genotyping Method: Patients were screened for 10 known mutations using PCR and restriction enzymes and all 14 exons of the IDUA gene were amplified and analyzed by single strand conformational polymorphism (SSCP) analysis. PCRs were performed and sequenced using the big dye terminator kit and an ABI 373 automated sequencer (Applied Biosystems). Mutations were confirmed by sequencing the reverse strand using the same method.
PreviouslyPublished: n/a
Variant: allele 1: M133I/ Y202X (father); allele 2: 678 G→A (mother)
other changes: A8, A20, Q33H, L118
ClinVar: CA355961907