POMT1 and POMT2 mutations in CMD patients: A multicentric Italian study S. Messina a,b , M. Mora c , E. Pegoraro d , A. Pini e , T. Mongini f , A. D’Amico g , M. Pane a , C. Aiello g , C. Bruno h , R. Biancheri h , A. Berardinelli i , C. Boito d , L. Farina c , L. Morandi c , I. Moroni c , R. Pezzani d , A. Pichiecchio i , E. Ricci j , A. Ruggieri c , S. Saredi c , C. Scuderi k , A. Tessa g , A. Toscano b , G. Tortorella l , C.P. Trevisan d , C. Uggetti i , F.M. Santorelli g , E. Bertini g , E. Mercuri a,m, * a Department of Paediatric Neurology, Catholic University, Policlinico Gemelli, 00168 Rome, Italy b Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy c Myopathology and Neuroimmunolgy, Pediatric Neurology and Neuroradiology Units, Neurological Institute C. Besta, Milan, Italy d Department of Neurosciences, University of Padua, Padua, Italy e Child Neurology and Psychiatry Unit, Maggiore Hospital, Bologna, Italy f Neuromuscular Center, S.G. Battista Hospital, University of Turin, Italy g Department of Laboratory Medicine, Unit of Molecular Medicine, Bambino Gesu ` Hospital, Rome, Italy h Neuromuscular Disease Unit, G. Gaslini Institute, Genoa, Italy i IRCCS ‘‘C. Mondino ” Foundation, University of Pavia, Pavia, Italy j Institute of Neurology, Catholic University, Policlinico Gemelli, Rome, Italy k IRCCS Oasi Maria SS, Neurological Unit, Troina, Italy l Unit of Child Neuropsychiatry, Department of Medical and Surgical Pediatrics, University of Messina, Messina, Italy m Dubowitz Neuromuscular Centre, Department of Paediatrics, Imperial College, Hammersmith Hospital, London, UK Received 3 November 2007; received in revised form 8 March 2008; accepted 2 April 2008 Abstract Mutations in POMT1 and POMT2 genes were originally identified in Walker–Warburg syndrome (WWS) and subsequently in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without oc mations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystro patients with a-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known f with a-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occu patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutat and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in pa mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypopla also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with f cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible f the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 and the spectrum of associated phenotypes is wider than initially thought. Ó 2008 Elsevier B.V. All rights reserved. 0960-8966/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2008.04.004 * Corresponding author. Address: Department of Child Neurology, Policlinico Gemelli, Largo Gemelli 00168, Rome, Italy. Tel.: +39 06 3015 +39 06 30154363. E-mail address: mercuri@rm.unicatt.it (E. Mercuri). www.elsevier.com/locate/nmd Neuromuscular Disorders 18 (2008) 565–571