RT Journal Article SR Electronic T1 Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 179 OP 183 DO 10.1136/jmedgenet-2011-100542 VO 49 IS 3 A1 Marjolein H Willemsen A1 Lisenka E L Vissers A1 Michèl A A P Willemsen A1 Bregje W M van Bon A1 Thessa Kroes A1 Joep de Ligt A1 Bert B de Vries A1 Jeroen Schoots A1 Dorien Lugtenberg A1 Ben C J Hamel A1 Hans van Bokhoven A1 Han G Brunner A1 Joris A Veltman A1 Tjitske Kleefstra YR 2012 UL http://jmg.bmj.com/content/49/3/179.abstract AB Background DYNC1H1 encodes the heavy chain protein of the cytoplasmic dynein 1 motor protein complex that plays a key role in retrograde axonal transport in neurons. Furthermore, it interacts with the LIS1 gene of which haploinsufficiency causes a severe neuronal migration disorder in humans, known as classical lissencephaly or Miller-Dieker syndrome.Aim To describe the clinical spectrum and molecular characteristics of DYNC1H1 mutations.Methods A family based exome sequencing approach was used to identify de novo mutations in patients with severe intellectual disability.Results In this report the identification of two de novo missense mutations in DYNC1H1 (p.Glu1518Lys and p.His3822Pro) in two patients with severe intellectual disability and variable neuronal migration defects is described.Conclusion Since an autosomal dominant mutation in DYNC1H1 was previously identified in a family with the axonal (type 2) form of Charcot- Marie-Tooth (CMT2) disease and mutations in Dync1h1 in mice also cause impaired neuronal migration in addition to neuropathy, these data together suggest that mutations in DYNC1H1 can lead to a broad phenotypic spectrum and confirm the importance of DYNC1H1 in both central and peripheral neuronal functions.