title: Monozygotic twins with a de novo 0.32 Mb 16q24.3 deletion, including TUBB3 presenting with developmental delay and mild facial dysmorphism but without overt brain malformation.
abstract: Nervous system development is highly dependent on the function of microtubules, which are assembled from tubulin heterodimers containing several α- and β-tubulin isotypes encoded by separate genes. A spectrum of neurological disorders with malformations of the central nervous system has recently been associated with missense mutations in this group of genes. Here, we report two patients, monozygotic twins, carrying a de novo 0.32 Mb deletion of chromosome 16q24.3 including the TUBB3 gene. The patients presented with global developmental delay, mild facial dysmorphism, secondary microcephaly, and mild spastic diplegia. Cerebral magnetic resonance imaging of the patients did not reveal cortical malformations, malformations of the corticospinal tracts, basal ganglia, corpus callosum, or optic nerves. This observation is in contrast to the group of neurological disorders that are associated with heterozygous missense mutations in genes encoding different neuronal α- and β-tubulin isotypes, termed tubulinopathies. On the background of current knowledge regarding the function and genotype-phenotype correlations of mutations in the neuronal tubulin isotypes, the clinical and diagnostic findings in these patients are discussed. To our knowledge, this is the first report of patients with a de novo deletion of the TUBB3 gene. The lack of cortical or other cerebral malformations supports the current hypothesis that TUBB3-related tubulinopathies are caused by altered protein function.
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Sabine
authors.initials: S
authors.lastname: Grønborg
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kjaergaard
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Hove
authors.affiliation: Department of Neuroradiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Vibeke André
authors.initials: VA
authors.lastname: Larsen
authors.affiliation: Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Kirchhoff
mesh_terms: D020029:Base Pairing / Q000235:genetics*; D001921:Brain / Q000002:abnormalities*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000235:genetics*; D019066:Facies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D017384:Sequence Deletion; D014404:Tubulin / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: C498585:TUBB3 protein, human; D014404:Tubulin
keywords: TUBB3; tubulin genes; tubulinopathies