TY - JOUR T1 - A complex deletion-inversion-deletion event results in a chimeric <em>IL1RAPL1</em>-dystrophin transcript and a contiguous gene deletion syndrome JF - Journal of Medical Genetics JO - J Med Genet SP - 127 LP - 131 DO - 10.1136/jmg.40.2.127 VL - 40 IS - 2 AU - J M Wheway AU - S C Yau AU - V Nihalani AU - D Ellis AU - M Irving AU - M Splitt AU - R G Roberts Y1 - 2003/02/01 UR - http://jmg.bmj.com/content/40/2/127.abstract N2 - 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. Clinical description The patient was the second child of healthy, non-consanguineous parents (father 39 years old, mother 17). He was well in the immediate neonatal period, but collapsed at 17 hours with profound hypoglycaemia. In spite of intravenous dextrose, he had a cardiopulmonary arrest. Resuscitation required several doses of intravenous epinephrine and he eventually responded to intravenous hydrocortisone. Subsequently, he required artificial ventilation for four days. Following resuscitation, he was found to be hyponatraemic and ultrasound scanning failed to identify the adrenal glands. Further investigation showed glycerol kinase deficiency (0.3 nmol/h/mg protein in cultured skin fibroblasts), an undetectable … ER -