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.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Willemsen MH,Vissers LE,Willemsen MA,van Bon BW,Kroes T,de Ligt J,de Vries BB,Schoots J,Lugtenberg D,Hamel BC,van Bokhoven H,Brunner HG,Veltman JA,Kleefstra Tdoi
10.1136/jmedgenet-2011-100542subject
Has Abstractpub_date
2012-03-01 00:00:00pages
179-83issue
3eissn
0022-2593issn
1468-6244pii
jmedgenet-2011-100542journal_volume
49pub_type
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