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Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Introduction: Theory of mind (ToM) is important for social interactions and typical development and has been found to be impaired in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Hypoactivation in frontotemporal brain regions seems to be the underlying neural mechanism in AN while whole-brain analyses in BN are lacking.
Methods: We used the well-validated social recognition task fMRI paradigm to assess ToM in a total of 72 female adolescents (16 BN, 18 AN and 38 matched healthy controls [HC]).
Results: Compared to HCBN, patients with BN showed hyperactivity during ToM-activity in the right frontal pole, middle temporal gyrus and left temporal pole and differed fundamentally from hypoactivation in these regions observed in patients with AN before and after short-term weight rehabilitation. Interaction and overlap analyses confirmed that similar regions were affected in opposite directions in both diseases. Hyperactivations in BN in the right middle temporal gyrus and right frontal pole were associated with clinical BN-severity markers binging and purging frequency.
Discussion: The hyperactivation in BN suggest different underlying neural mechanisms for ToM compared to AN. Hyperactivity might correspond to a different but also ineffective cognitive style in patients with BN when approaching social interactions. These important transdiagnostic differences are relevant for future brain-targeted therapeutic approaches.
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.