Mucopolysaccharidosis type I: identification of novel mutations that cause Hurler/Scheie syndrome in Chinese families

The complementary and genomic DNA segments of the alpha-L-iduronidase gene from two Chinese mucopolysaccharidosis type I Hurler/Scheie (IMPS WS) patients were amplified by polymerase chain reaction (PCR) and DNA sequencing was done to study their molecular lesions. Patient W3 has heterozygous mutations; the maternal allele has M1I (G to A transition in the initiation codon ATG) and the paternal allele has Y343X (C to G transversion in exon 8 leading to in frame deletion of codons 325-343 from the mRNA owing to false splicing). Patient W2 is homozygous for mutation T364M (C to T transition in codon 364). The mutation was paternally inherited. A de novo deletion or gene conversion event may have resulted in apparent homozygosity for T364M. Expression of Y343X and T364M showed trace amounts of alpha-L-iduronidase activity compared to that of normal cDNA upon transfection into COS-7 cells.