key: cord-0012915-cuvctznf
authors: Nambot, Sophie; Hevner, Robert F.; Dobyns, William B.
title: Reply to Hsueh YP et al.
date: 2020-04-09
journal: Eur J Hum Genet
DOI: 10.1038/s41431-020-0622-z
sha: 4d7996f4cb42cfe21bbc77692e86b878ad7dfae4
doc_id: 12915
cord_uid: cuvctznf

nan

We thank Hsueh et al. for their interest in our article, and for their comments emphasizing the significance of anterior commissure (AC) hypoplasia/agenesis as a common feature in TBR1 deficient mice and humans. We agree that our statement about AC defects not having been previously reported in mice or humans with TBR1 alterations was mistaken, and we regret this inadvertent oversight. In fact, our main goal was to draw attention to the novel hippocampal dysgenesis that we observed in TBR1 deficient mice and humans [1] , which could impact learning and memory.

Severe defects of the AC (anterior and posterior limbs) were originally reported 19 years ago in homozygous Tbr1 −/− mice [2] . More recently, the Hsueh group made important novel contributions showing that heterozygous Tbr1 +/− mice also had AC defects, primarily agenesis/ hypoplasia of the posterior limb of the AC [3] , along with subtle hypoplasia of the anterior AC [4] . Thus, AC defects are shared among heterozygous [3, 4] and homozygous [2] Tbr1 mutant mice, as well as humans with heterozygous TBR1 mutations/haploinsufficiency [1] .

The hypothesis that abnormal connections of the amygdala, including deficient posterior AC connections, may contribute to autism-related behavioral problems in TBR1 deficient mice and humans [3] is interesting. On the other hand, the neocortical and hippocampal dysgenesis documented in many TBR1 patients [1] indicates that TBR1 deficiency has widespread effects on cortical as well as amygdala development. We fully agree that novel therapeutic approaches, such as treatment with D-cycloserine, should be investigated for patients with the TBR1 neurocognitive phenotype.

Conflict of interest The authors declare that they have no conflict of interest.

Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits: report of 25 new individuals and review of the literature

Tbr1 regulates differentiation of the preplate and layer 6

Tbr1 haploinsufficiency impairs amygdalar axonal projections and results in cognitive abnormality

Haploinsufficiency of autism causative gene Tbr1 impairs olfactory discrimination and neuronal activation of the olfactory system in mice