Title: | Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects |
Author(s): | Willemsen, M.H. ; Peart-Vissers, L.E.L.M. ; Willemsen, M.A.A.P. ; van Bon, B.W. ; Kroes, T.; de Ligt, J.; Vries, L.B.A. de ; Schoots, J.; Lugtenberg, D. ; Hamel, B.C.J. ; Bokhoven, J.H.L.M. van ; Brunner, H.G. ; Veltman, J.A. ; Kleefstra, T. |
Publication year: | 2012 |
Source: | Journal of Medical Genetics, vol. 49, iss. 3, (2012), pp. 179-183 |
ISSN: | 0022-2593 |
DOI: | https://doi.org/10.1136/jmedgenet-2011-100542 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/108771 ![]() |
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Subject: | DCN MP - Plasticity and memory IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 3: Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory NCEBP 7: Effective primary care and public health NCMLS 6: Genetics and epigenetic pathways of disease DCN MP - Plasticity and memory NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disorders |
Organization: | Primary and Community Care Human Genetics Paediatrics - OUD tm 2017 Neurology |
Journal title: |
Journal of Medical Genetics
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Volume: | vol. 49 |
Issue: | iss. 3 |
Page start: | p. 179 |
Page end: | p. 183 |
Abstract: |
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.
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