Open AccessInvestigation of TBR1 Hemizygosity: Four Individuals with 2q24 Microdeletions
Author(s) -
Ryan N Traylor,
William B. Dobyns,
Jill A. Rosenfeld,
Patricia G. Wheeler,
J. Edward Spence,
Anne M. Bandholz,
Erawati V. Bawle,
Erin P. Carmany,
Cynthia M. Powell,
Beth Hudson,
Roger A. Schultz,
LG Shaffer,
BC Ballif
Publication year - 2012
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000342008
Subject(s) - autism spectrum disorder , ventriculomegaly , kaliuresis , neuroscience , genetics , biology , medicine , autism , psychiatry , fetus , pregnancy , kidney , diuresis
TBR1 encodes a transcription factor with critical roles in corticogenesis, including cortical neuron migration and axon pathfinding, establishment of regional and laminar identity of cortical neurons, and control of glutamatergic neuronal cell fate. Based upon TBR1's role in cortical development, we sought to investigate TBR1 hemizygosity in individuals referred for genetic evaluation of intellectual disability and developmental delay. We describe 4 patients with microdeletions identified by molecular cytogenetic techniques, encompassing TBR1 and spanning 2q24.1q31.1, ranging in size from 2.17 to 12.34 Mb. Only the patient with the largest deletion had a possible cortical malformation. Mild ventriculomegaly is the only common brain anomaly, present in all patients; a Chiari I malformation is seen in 2 patients, and mega cisterna magna is seen in a third. Our findings are consistent with Tbr1 mouse models showing that hemizygosity of the gene requires additional genetic factors for the manifestation of severe structural brain malformations. Other syndromic features are present in these patients, including autism spectrum disorders, ocular colobomas, and craniosynostosis, features that are likely affected by the deletion of genes other than TBR1.