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Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder. A novel gross deletion in the iduronate-2-sulfatase (IDS) gene was found in a 6-year-old boy with Hunter syndrome. The phenotype of the patient was severe, including joint stiffness, kyphosis, hepatomegaly, hypertrophic cardiomyopathy, moderate mental retardation, and bilateral hearing loss. The 38.8 kb gross deletion involves exons 1-7, the proximal breakpoints lying in intron 7, at position 1307880 (GenBank NT:019686), and the distal deletion breakpoint was located at position 1346697. The large deletion correlated with the severe phenotype of this Hunter syndrome patient.

Hypophosphatemic rickets is a genetic disorder commonly associated with renal phosphate wasting and bone deformities. The PHEX gene (phosphate regulating gene with homologies to endopeptidases on the X chromosome) encodes a 749-amino acid protein that putatively consists of an intracellular, transmembrane, and extracellular domain. PHEX mutations have been observed in 60-80% of hypophosphatemic rickets patients. In this study, we report 2 de novo novel mutations in 2 Taiwanese girls with clinical characteristics of hypophosphatemic rickets. The presenting phenotype of lower extremity deformities and short stature was suggestive of the diagnosis. Primers flanking 22 exons were used to amplify DNA by polymerase chain reaction. The results by direct DNA sequencing of case 1 revealed a C to T transition changing glutamine at codon 224 in exon 6 to a stop codon (Q224X). The result of case 2 showed a 2-base pair deletion (2090delGA) and resulted in a frameshift and premature termination of codon (PTC+19aa). Both mutations presumably result in a truncated protein, leading to loss of function of PHEX. This is the first report of PHEX gene mutation in the Taiwanese population.

Russell-Silver syndrome (RSS) should be suspected in patients with prenatal and postnatal growth retardation. Because there is no clinical feature specific for RSS, molecular analysis is necessary to confirm the diagnosis. Recently, maternal uniparental disomy of chromosome 7 (mUPD7) has been reported in approximately 10% of RSS patients. We describe a 10-year-old Taiwanese RSS girl with prenatal and postnatal growth retardation, relative macrocephaly, a triangular face, frontal bossing, and mild fifth finger clinodactyly. Molecular diagnosis of mUPD7 was confirmed by use of methylation-specific polymerase chain reaction and haplotype analysis with single nucleotide polymorphisms (SNPs) genotyping. Analyzing the methylation status of the PEG1/MEST gene is a cost-effective screening method for mUPD7 molecular diagnosis. However, positive cases should be subsequently confirmed by haplotype analysis using SNPs genotyping or short tandem repeat markers.