Infantile nephropatic cystinosis is a rare, recessive, and genetically homogeneous disorder impairing renal function. It is caused by mutations in CTNS. Several large copy number aberrations have been identified but, for the majority of these, heterozygous patients and carriers can not easily be identified. We therefore developed a multiplex ligation-dependent probe amplification assay targeting eight of the twelve CTNS exons. We show that this assay is valid in detecting known deletions in both the homozygous and heterozygous state. The application to a family previously found mutation-negative by conventional screening revealed a novel large deletion which, as the first of its kind, does not involve the coding region. We conclude that our assay represents a valid tool for further completing the CTNS mutation spectrum and for simplified carrier testing in cystinosis families harboring copy number mutations. More generally, our study exemplifies the use of synthetic, homemade MLPA probesets as cheap, efficient, and rapidly available screening tools for small genes and/or very rare diseases.
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