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.
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.
Authors: Matthew G Marzo; Jacqueline M Griswold; Kristina M Ruff; Rachel E Buchmeier; Colby P Fees; Steven M Markus Journal: Elife Date: 2019-07-31 Impact factor: 8.140
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Authors: Alexander M Rossor; Emily C Oates; Hannah K Salter; Yang Liu; Sinead M Murphy; Rebecca Schule; Michael A Gonzalez; Mariacristina Scoto; Rahul Phadke; Caroline A Sewry; Henry Houlden; Albena Jordanova; Iyailo Tournev; Teodora Chamova; Ivan Litvinenko; Stephan Zuchner; David N Herrmann; Julian Blake; Janet E Sowden; Gyuda Acsadi; Michael L Rodriguez; Manoj P Menezes; Nigel F Clarke; Michaela Auer Grumbach; Simon L Bullock; Francesco Muntoni; Mary M Reilly; Kathryn N North Journal: Brain Date: 2014-12-14 Impact factor: 13.501
Authors: Michele L Yang; Jimann Shin; Christina A Kearns; Melissa M Langworthy; Heather Snell; Macie B Walker; Bruce Appel Journal: Dev Dyn Date: 2015-02 Impact factor: 3.780