Expanding the Neuropsychological Phenotype of KAT6B Disorders: Overlapping Features with KAT6A Syndrome.

KAT6B and KAT6A belong to the MYST family of lysine acetyltransferases, and regulate gene expression via histone modification. Although both proteins share similar structure and epigenetic regulatory functions, it remains unclear if KAT6A/6B mutation disorders, both very rare conditions, yield the same neurocognitive presentation and thus benefit from similar treatment approaches. This study provides a preliminary overview of neuropsychological functioning of 13 individuals with KAT6B disorder (Mean age = 9.

Neuropsychological profile associated with KAT6A syndrome: Emergent genotype-phenotype trends.

Background: KAT6A (Arboleda-Tham) syndrome is a Mendelian disorder of the epigenetic machinery caused by pathogenic variants in the lysine acetyltransferase 6 A (KAT6A) gene. Intellectual disability and speech/language impairment (e.g.

KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.

Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years.

The social phenotype associated with Wiedemann-Steiner syndrome: Autistic traits juxtaposed with high social drive and prosociality.

The aim of this study was to provide a descriptive overview of the social characteristics associated with Wiedemann-Steiner syndrome (WSS). A total of 24 parents of children/adults with WSS (11F, mean age = 12.94 years, SD = 8.

Epigenetics of cognition and behavior: insights from Mendelian disorders of epigenetic machinery.

Epigenetics, one mechanism by which gene expression can change without any changes to the DNA sequence, was described nearly a century ago. However, the importance of epigenetic processes to neurodevelopment and higher order neurological functions like cognition and behavior is only now being realized. A group of disorders known as the Mendelian disorders of the epigenetic machinery are caused by the altered function of epigenetic machinery proteins, which consequently affects downstream expression of many genes.

Neurobehavioral phenotype of Kabuki syndrome: Anxiety is a common feature.

Kabuki syndrome (KS) is a Mendelian Disorder of the Epigenetic Machinery (MDEM) caused by loss of function variants in either of two genes involved in the regulation of histone methylation, (34-76%) or (9-13%). Previously, representative neurobehavioral deficits of KS were recapitulated in a mouse model, emphasizing the role of KMT2D in brain development, specifically in ongoing hippocampal neurogenesis in the granule cell layer of the dentate gyrus. Interestingly, anxiety, a phenotype that has a known association with decreased hippocampal neurogenesis, has been anecdotally reported in individuals with KS.

Sleep disturbance is a common feature of Kabuki syndrome.

Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire.

Leveraging the Mendelian disorders of the epigenetic machinery to systematically map functional epigenetic variation.

Although each Mendelian Disorder of the Epigenetic Machinery (MDEM) has a different causative gene, there are shared disease manifestations. We hypothesize that this phenotypic convergence is a consequence of shared epigenetic alterations. To identify such shared alterations, we interrogate chromatin (ATAC-seq) and expression (RNA-seq) states in B cells from three MDEM mouse models (Kabuki [KS] type 1 and 2 and Rubinstein-Taybi type 1 [RT1] syndromes).

Modeling Liver Organogenesis by Recreating Three-Dimensional Collective Cell Migration: A Role for TGFβ Pathway.

Three-dimensional (3D) collective cell migration (CCM) is critical for improving liver cell therapies, eliciting mechanisms of liver disease, and modeling human liver development and organogenesis. Mechanisms of CCM differ in 2D vs. 3D systems, and existing models are limited to 2D or transwell-based systems, suggesting there is a need for improved 3D models of CCM.