1. TUBB4A de novo mutations cause isolated hypomyelination
- Author
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Pizzino, Amy, Pierson, Tyler Mark, Guo, Yiran, Helman, Guy, Fortini, Sebastian, Guerrero, Kether, Saitta, Sulagna, Murphy, Jennifer Louise Patrick, Padiath, Quasar, Xie, Yi, Hakonarson, Hakon, Xu, Xun, Funari, Tara, Fox, Michelle, Taft, Ryan J, van der Knaap, Marjo S, Bernard, Geneviève, Schiffmann, Raphael, Simons, Cas, and Vanderver, Adeline
- Subjects
Pediatric ,Congenital Structural Anomalies ,Neurosciences ,Brain Disorders ,Genetics ,Clinical Research ,Rare Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Adolescent ,Atrophy ,Basal Ganglia ,Cerebellum ,Child ,Child ,Preschool ,Exome ,Female ,Hereditary Central Nervous System Demyelinating Diseases ,Humans ,Magnetic Resonance Imaging ,Male ,Middle Aged ,Mutation ,Phenotype ,Registries ,Tubulin ,Clinical Sciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
ObjectiveWe present a series of unrelated patients with isolated hypomyelination, with or without mild cerebellar atrophy, and de novo TUBB4A mutations.MethodsPatients 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.ResultsFive 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.ConclusionHypomyelinating 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.
- Published
- 2014