BACKGROUND: Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. METHOD: Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. RESULTS: 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. CONCLUSION: Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.
BACKGROUND: Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. METHOD: Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. RESULTS: 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. CONCLUSION: Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.
Authors: Lisenka E L M Vissers; Conny M A van Ravenswaaij; Ronald Admiraal; Jane A Hurst; Bert B A de Vries; Irene M Janssen; Walter A van der Vliet; Erik H L P G Huys; Pieter J de Jong; Ben C J Hamel; Eric F P M Schoenmakers; Han G Brunner; Joris A Veltman; Ad Geurts van Kessel Journal: Nat Genet Date: 2004-08-08 Impact factor: 38.330
Authors: Thomas S Scerri; Anna Quaglieri; Carolyn Cai; Jana Zernant; Nori Matsunami; Lisa Baird; Lea Scheppke; Roberto Bonelli; Lawrence A Yannuzzi; Martin Friedlander; Catherine A Egan; Marcus Fruttiger; Mark Leppert; Rando Allikmets; Melanie Bahlo Journal: Nat Genet Date: 2017-02-27 Impact factor: 38.330
Authors: Zehra Ordulu; Tammy Kammin; Harrison Brand; Vamsee Pillalamarri; Claire E Redin; Ryan L Collins; Ian Blumenthal; Carrie Hanscom; Shahrin Pereira; India Bradley; Barbara F Crandall; Pamela Gerrol; Mark A Hayden; Naveed Hussain; Bibi Kanengisser-Pines; Sibel Kantarci; Brynn Levy; Michael J Macera; Fabiola Quintero-Rivera; Erica Spiegel; Blair Stevens; Janet E Ulm; Dorothy Warburton; Louise E Wilkins-Haug; Naomi Yachelevich; James F Gusella; Michael E Talkowski; Cynthia C Morton Journal: Am J Hum Genet Date: 2016-10-13 Impact factor: 11.025
Authors: Alex R Paciorkowski; Judy Weisenberg; Joshua B Kelley; Adam Spencer; Emily Tuttle; Dalia Ghoneim; Liu Lin Thio; Susan L Christian; William B Dobyns; Bryce M Paschal Journal: Eur J Hum Genet Date: 2013-09-18 Impact factor: 4.246
Authors: Rebecca A Chodroff; Leo Goodstadt; Tamara M Sirey; Peter L Oliver; Kay E Davies; Eric D Green; Zoltán Molnár; Chris P Ponting Journal: Genome Biol Date: 2010-07-12 Impact factor: 13.583