Molecular Analyses in Families with Hunter Syndrome Indicate Unequal Male and Female Mutation Rates in the Iduronate-2-Sulfatase Gene

Copyright: © 2014 Peining Li, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Molecular diagnosis for patients with mucopolysaccharidosis type II (MPS II, Hunter syndrome) has detected a spectrum of mutations including large deletions, intragenic rearrangements, recurrent nucleotide substitutions at CpG sites, and high proportion of novel point mutations in the X-linked iduronate-2-sulfatase (IDS) gene. The mutational heterogeneity and the X-linked inheritance make the IDS gene a good disease model for studying human germline mutations and underlying mechanisms. Pooling data from 135 MPS II families observed that 8 % were sporadic cases from de novo maternal germline mutations and 92 % were transmitted cases from carrier females. Haplotyping analysis on transmitted cases showed preference of germline mutations from maternal grandfather. Estimation of male-to-female ratio of mutation rates indicated a 3.76-to-10.5-fold higher mutation rate in males for mutations in the IDS gene. However, little is known on gender-specific mutation rate for different type of mutations in the IDS gene. A large-scale population based collaborative study to construct a database of detailed mutational composition and family pedigrees is needed to further characterize the mutation origin and male/female mutation rates in the IDS gene. This information will be helpful in genetic counseling and disease prevention and also gain insight into mutagenesis mechanisms for various types of mutations