Deletion mapping in Xp21 for patients with complex glycerol kinase deficiency using SNP mapping arrays

Infantile or complex glycerol kinase deficiency (cGKD) is a contiguous gene deletion syndrome caused by a loss of GK (MIM# 300474), along with its neighboring genes, Duchenne muscular dystrophy (DMD; MIM# 300377) and/or Nuclear Receptor Subfamily 0, Group B, Member 1 (NR0B1; MIM# 300473). Patients with cGKD present with glyceroluria and hyperglycerolemia in association with DMD and/or adrenal hypoplasia congenita (AHC). The purpose of these investigations was to determine whether the Affymetrix GeneChip Mapping Array (SNP chip) could be utilized to detect and map breakpoints in patients with cGKD. Genomic DNAs from several primary lymphoblastoid cell lines from patients with cGKD were analyzed on the Affymetrix platform. The Affymetrix SNP chip is a high-density oligonucleotide array that allows a standardized, parallel interrogation of thousands of SNPs across the entire genome (except for the Y chromosome). Analysis of the array features' hybridization intensities enabled clear delineation of the patient deletions with a high degree of confidence. Many of these patient deletions had been mapped by PCR and their breakpoints confirmed by sequencing. This study demonstrates the utility of the Affymetrix Mapping GeneChips for molecular cytogenetic analysis, beyond the SNP genotyping for which the arrays were initially designed. With one out of 160 live births (approximately 25,000 U.S. neonates annually) reported to have cytogenetic disorders, we envision a significant need for such a standardized platform to carry out rapid, high-throughput, genomic analyses for molecular cytogenetics applications.