ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:1581–1586 (2008) Clinical Report Interstitial Deletion of 1p22.2p31.1 and Medium-Chain Acyl-CoA Dehydrogenase Deficiency in a Patient With Global Developmental Delay Gustavo H.B. Maegawa, 1,2,3 * Nicola K. Poplawski, 4 Brage Storstein Andresen, 5 Simon E. Olpin, 6 Gloria Nie, 2 Joe T.R. Clarke, 1,2,3,7,8 and Ikuko Teshima 2,3 1 Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada 2 Division of Clinical and Metabolic Genetics, Hospital for Sick Children, Toronto, Ontario, Canada 3 Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada 4 Department of Genetic Medicine, Women’s and Children’s Hospital, North Adelaide, Australia 5 Research Unit for Molecular Medicine, Institute of Human Genetics, Aarhus University, Aarhus, Denmark 6 Department of Clinical Chemistry, Sheffield Children’s Hospital, Sheffield, UK 7 Division of Molecular Genetics, Hospital for Sick Children, Toronto, Ontario, Canada 8 Centre Hospitalier Universitaire de Sherbrooke, Hpital Fleurimont, Service de Ge ´ne ´tique, Sherbrooke, Que ´bec, Canada Received 2 August 2007; Accepted 21 December 2007 We report on a 6-year-old girl who presented at 6 months of age with seizures, delayed psychomotor development and mild facial dysmorphism. A small muscular ventricular septal defect was documented on echocardiogram and brain MRI showed a frontal brain anomaly. Urine organic acid analysis revealed dicarboxylic aciduria, and plasma acylcarnitine analysis showed marked elevation of octanoyl (C8) and decanoyl (C10) carnitines with C8:C10 ratio of 9:1. These results were indicative of medium chain acyl-CoA dehydro- genase deficiency. ACADM gene sequencing showed an apparent homozygous c.166G > C (Ala31Pro) missense mutation in exon 3; however, only the mother was found to be a carrier of this novel missense mutation. This finding along with non-regressive developmental delay prompted further karyotype and genomic investigations. An interstitial deletion of chromosome 1 was detected by repeat G- banding: 46,XX,del(1)(p22.2p31.1). Parental karyotypes were normal. The deletion was characterized by array CGH analysis using a 1 Mb BAC/PAC array platform. Clones deleted extended from RP11-88B10 (1p31.1) to RP5- 1007M22 (1p22.2), a 15.5 Mb deletion which includes the ACADM locus. Clinical review of 6/7 cases of interstitial deletions with breakpoints of 1p22 and 1p31/32, including the patient in this report, indicate a variable phenotype. Thus, although G-band breakpoints are similar, common breakpoints for these alterations are unlikely. This is the first report of a patient with fatty acid oxidation defect caused by a mutation in combination with an interstitial chromosomal deletion. ß 2008 Wiley-Liss, Inc. Key words: medium-chain acyl-CoA dehydrogenase defi- ciency; chromosome 1; interstitial deletion How to cite this article: Maegawa GHB, Poplawski NK, Andresen BS, Olpin SE, Nie G, Clarke JTR, Teshima I. 2008. Interstitial deletion of 1p22.2p31.1 and medium-chain acyl-CoA dehydrogenase deficiency in a patient with global developmental delay. Am J Med Genet Part A 146A:1581 – 1586. INTRODUCTION Interstitial deletions of chromosome 1 short arm are relatively rare [Stockton et al., 1997; Mircher et al., 2003]. Most reports describe individuals with a moderate neurological and dysmorphic phenotype. Herein we report on a 6-year-old girl who was initially diagnosed with medium-chain acyl-CoA de- hydrogenase deficiency (MCADD; OMIM *607008), and was later found to carry an interstitial deletion of chromosome 1 between bands 1p22.2 and 1p31.1 Abbreviation used: MCADD, medium-chain Acyl-CoA dehydrogenase deficiency; FAOD, fatty acid oxidation defects; VSD, ventricular septal defect; array CGH, array-based comparative genomic hybridization. *Correspondence to: Gustavo H.B. Maegawa, M.D., FCCMG, FACMG, Division of Clinical and Metabolic Genetics, Department of Paediatrics, Genetics and Genomic Biology, Research Institute, Rm. 9143, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8. E-mail: gustavo.maegawa@sickkids.ca DOI 10.1002/ajmg.a.32255