• dystrophin
• glycerol kinase
• adrenal hypoplasia
• inversion

We originally identified the IL1RAPL1 gene through its partial deletion in a patient with Becker muscular dystrophy (BMD), glycerol kinase deficiency (GKD), adrenal hypoplasia congenita (AHC), and mild mental retardation,¹ and suggested that its disruption might account for the patient’s cognitive problems. Other workers have shown that intragenic mutations of the IL1RAPL1 gene are associated with mild, non-specific X linked mental retardation.²IL1RAPL1 encodes a putative transmembrane cytokine receptor related to receptors and receptor accessory proteins for interleukin-1 and -18, and is expressed in brain and muscle.³ The protein structure comprises three extracellular immunoglobulin domains, which presumably mediate binding of an as yet unidentified ligand, a transmembrane region, and an intracellular domain, which is likely to enable signalling via the NFκB pathway. Its role in brain development or function is not understood.

We describe here the precise structure of a complex deletion-inversion-deletion mutation involving more than 2 Mb of Xp21 in a patient with a contiguous gene deletion syndrome. This results in the loss of several genes and the creation of an unusual fusion of the IL1RAPL1 and dystrophin genes with the potential to generate a chimeric protein product. We discuss the possible mutational mechanisms and biological consequences of this rearrangement.