Novel TUBB4A mutations and expansion of the neuroimaging phenotype of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC)

Carlos Ferreira, Andrea Poretti, Julie Cohen, Ada Hamosh, Sakkubai Naidu

Research output: Contribution to journalArticlepeer-review

Abstract

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) has recently been associated with a single heterozygous p.D249N mutation in TUBB4A. We describe two novel mutations in this gene. A p.C239F mutation was found in one of the originally described H-ABC patients, for whom we provide follow-up 11 years after the original publication. The second novel mutation, p.R262H, was found in a patient with a typical clinical presentation for H-ABC, but with a novel neuroimaging phenotype, given the absence of atrophy of the putamen and caudate nucleus despite 7 years of follow-up. The recent recognition of TUBB4A mutations as the underlying etiology of H-ABC will likely lead to the identification of subtler clinical and neuroimaging presentations of this disorder, like in our third patient. Thus mutations in this gene should be suspected in any patient with hypomyelination, regardless of the long-term presence of neostriatal atrophy.

Original languageEnglish (US)
Pages (from-to)1802-1807
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • Hypomyelination with atrophy of the basal ganglia and cerebellum
  • TUBB4A
  • Tubulin beta 4

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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