title: Congenital Cataracts and Gut Dysmotility in a DYNC1H1 Dyneinopathy Patient.
abstract: Whole exome sequencing continues to end the diagnostic odyssey for a number of patients and expands our knowledge of phenotypes associated with gene mutations. We describe an 11-year-old female patient with a constellation of symptoms including congenital cataracts, gut dysmotility, sensory neuropathy, and bifrontal polymicrogyria. Whole exome sequencing was performed and identified a de novo heterozygous missense mutation in the ATPase motor domain ofcytoplasmic dynein heavy chain 1(DYNC1H1), which is known to be involved in neuronal migration and retrograde axonal transport. The mutation was found to be highly damaging by multiple prediction programs. The residue is highly conserved, and reported mutations in this gene result in a variety of phenotypes similar to that of our patient. We report only the second case of congenital cataracts and the first of gut dysmotility in a patient withDYNC1H1, thus expanding the spectrum of disease seen inDYNC1H1dyneinopathies.
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Rose.Gelineau.Morel@cchmc.org.
authors.forename: Rose
authors.initials: R
authors.lastname: Gelineau-Morel
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Marshall.Lukacs@cchmc.org.
authors.forename: Marshall
authors.initials: M
authors.lastname: Lukacs
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Kathryn.Weaver@cchmc.org.
authors.forename: K Nicole
authors.initials: KN
authors.lastname: Weaver
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Robert.hufnagel@nih.gov.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hufnagel
authors.affiliation: Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Donald.Gilbert@cchmc.org.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gilbert
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. rolf.stottmann@cchmc.org.|Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. rolf.stottmann@cchmc.org.
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Stottmann
keywords: cataracts; cortical development; dynein; gut dysmotility; polymicrogyria