title: TUBB4A de novo mutations cause isolated hypomyelination.
abstract: OBJECTIVE
  We present a series of unrelated patients with isolated hypomyelination, with or without mild cerebellar atrophy, and de novo TUBB4A mutations.
  
  
  METHODS
  Patients in 2 large institutional review board-approved leukodystrophy bioregistries at Children's National Medical Center and Montreal Children's Hospital with similar MRI features had whole-exome sequencing performed. MRIs and clinical information were reviewed.
  
  
  RESULTS
  Five patients who presented with hypomyelination without the classic basal ganglia abnormalities were found to have novel TUBB4A mutations through whole-exome sequencing. Clinical and imaging characteristics were reviewed suggesting a spectrum of clinical manifestations.
  
  
  CONCLUSIONS
  Hypomyelinating leukodystrophies remain a diagnostic challenge with a large percentage of unresolved cases. This finding expands the phenotype of TUBB4A-related hypomyelinating conditions beyond hypomyelination with atrophy of the basal ganglia and cerebellum. TUBB4A mutation screening should be considered in cases of isolated hypomyelination or hypomyelination with nonspecific cerebellar atrophy.
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Amy
authors.initials: A
authors.lastname: Pizzino
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Tyler Mark
authors.initials: TM
authors.lastname: Pierson
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Guy
authors.initials: G
authors.lastname: Helman
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fortini
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Kether
authors.initials: K
authors.lastname: Guerrero
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Saitta
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Jennifer Louise Patrick
authors.initials: JL
authors.lastname: Murphy
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Quasar
authors.initials: Q
authors.lastname: Padiath
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Tara
authors.initials: T
authors.lastname: Funari
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Michelle
authors.initials: M
authors.lastname: Fox
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Taft
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Bernard
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.affiliation: Authors' affiliations are listed at the end of the article.
authors.forename: Cas
authors.initials: C
authors.lastname: Simons
authors.affiliation: Authors' affiliations are listed at the end of the article. avanderv@childrensnational.org.
authors.forename: Adeline
authors.initials: A
authors.lastname: Vanderver
mesh_terms: D000293:Adolescent; D001284:Atrophy / Q000473:pathology; D001479:Basal Ganglia / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012042:Registries; D014404:Tubulin / Q000235:genetics*
chemical_list: C582076:TUBB4A protein, human; D014404:Tubulin
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