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Table 3 SUMF1 mutations identified in MSD patients

From: Natural disease history and characterisation of SUMF1 molecular defects in ten unrelated patients with multiple sulfatase deficiency

Patient Mutation Affected Exon Mutant protein Predicted effect of missense mutations on the FGE structure
1 c.[463 T > C] + [1029G > T] 3 and 9 p.[S155P] + [R343S] p.S155P: loss of three hydrogen bonds and steric clash with Ala186 [12]. p.R343S: direct interaction with both sulfhydryl groups of the catalytic Cys336/Cys341 pair. Might affect substrate binding and reactivity.
2 c.[836C > T] + [836C > T] 6 p.[A279V] + [A279V] Steric clash with Phe275 and Ala283 [12].
3 c.[836C > T] + [836C > T] 6 p.[A279V] + [A279V] Idem
4 c.[836C > T] + [836C > T] 6 p.[A279V] + [A279V] Idem
5 c.[893C > A] + [519 + 4A > G] 7 and 3 p.[A298E] + [A149_A173del, A175del] p.A298E: neither affects FGE fold nor binding to the Ca2+ ion at site 2.
6 c.[788G > T] + [788G > T] 6 p.[G263V] + [G263V] Steric clash with Thr263 and Thr270 [12].
7 c.[520_954dup (+) 520_954dup] 4 to 7 p.[V174_P318dup] + [V174_P318dup]  
8 c.[706C > T] + [1045C > T] 5 and 9 p.[R236X] + [R349W] p.R349W: loss of five interactions [12]. Should affect protein fold in the vicinity of the active site.
9 c.[132_133insG] + [1045C > T] 1 and 9 p.[V45fsX75] + [R349W] idem
10 c.[776A > G;1018 T > C] + [725 + 1G > C] 6, 9 and 5 p.[N259S; Y340H] + [P202_R242del] p.N259S precludes binding to Ca2+ ion at site 1. p.Y340H should not induce major structural changes.
  1. Novel mutations are indicated in bold characters. Patients are listed as in Table 1, where they are ranked on an ascending scale of disease severity.