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Worldwide distribution of common IDUA pathogenic variants
Author(s) -
Poletto E.,
Pasqualim G.,
Giugliani R.,
Matte U.,
Baldo G.
Publication year - 2018
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13224
Subject(s) - mucopolysaccharidosis type i , genotype , allele , genetics , allele frequency , population , biology , gene , medicine , disease , environmental health , enzyme replacement therapy
Mucopolysaccharidosis type I (MPS I) is a rare disorder caused by deleterious sequence variants in the α‐L‐iduronidase ( IDUA ) gene. More than 200 pathogenic variants have been described so far, but their frequencies have not yet been analyzed on a worldwide scale. To address this, we analyzed the genotypes of MPS I patients from 35 published studies papers. The most common pathogenic variant observed was p.Trp402Ter. With frequencies of up to 63%, it was the major allele in most European countries, America and Australia. The variant p.Gln70Ter was also frequent; it was found mainly in Northern and Eastern Europe. The most frequent variant in North African countries was p.Pro533Arg; in Morocco, it represented more than 90% of mutant alleles. Variants observed in East Asians were not found in Western populations, including c.1190‐1G>A, p.Ala79Val, p.Leu346Arg and c.613_617dupTGCTC. Conversely, p.Trp402Ter and p.Pro533Arg were not found in patients from East Asia. In conclusion, the most common pathogenic IDUA variant in MPS I patients are p.Trp402Ter, p.Gln70Ter and p.Pro533Arg. Knowledge about the genetic background of MPS I for each population is essential when developing new genotype‐targeted therapies, as well as to enable faster genetic analysis and improve patient management.