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Four novel mutations underlying mild or intermediate forms of α‐L‐iduronidase deficiency (MPS IS and MPS IH/S)
Author(s) -
Tieu Phuong T.,
Bach Gideon,
Matynia Anna,
Hwang Michael,
Neufeld Elizabeth F.
Publication year - 1995
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380060111
Subject(s) - hurler syndrome , mucopolysaccharidosis type i , mutation , mucopolysaccharidosis i , mucopolysaccharidosis , biology , phenotype , gene , compound heterozygosity , gene mutation , microbiology and biotechnology , genetics , enzyme replacement therapy , medicine , biochemistry , pathology , disease
The α‐L‐iduronidase deficiency diseases (Mucopolysaccharidosis I) cover a spectrum of clinical severity ranging from the very severe (Hurler syndrome, MPS IH) through an intermediate (Hurler/Scheie syndrome, MPS IH/S) to a relatively mild form (Scheie syndrome, MPS IS). Numerous mutations of the gene encoding α‐L‐iduronidase (IDUA) are known in Hurler syndrome, but only three in the other disorders. We report on novel mutations of the IDUA gene in one patient with the Scheie syndrome and in three patients with the Hurler/Scheie syndrome. The novel mutations, all single base changes, encoded the substitutions R492P (Scheie), and X654G, P496L, and L490P (Hurler/Scheie). The L490P mutation was apparently homozygous, whereas each of the others was found in compound hettrozygosity with a Hurler mutation. The deleterious nature of the mutations was confirmed by absence of enzyme activity upon transfection of the corresponding mutagenized cDNAs into Cos‐1 cells. These results provide additional information for genotype—phenotype correlations. © 1995 Wiley‐Liss, Inc.