KDM6A Haploinsufficiency Is Insufficient to Disrupt Cochlear Structure and Auditory Function in Mouse Models of Kabuki Syndrome Type 2

A patient-derived missense mouse model of Kabuki syndrome 1.

Kabuki syndrome type 1 (KS1) is a rare cause of intellectual disability resulting from heterozygous pathogenic variants in the gene encoding the histone methyltransferase KMT2D. A previously established loss-of-function mouse model of KS1 exhibits key phenotypic features, and therapeutic trials in this mouse model sugg...

DUOXA2-mediated thyroid hormone synthesis is indispensable for postnatal maturation of auditory function.

Cntnap2 deletion in mice causes developmentally transient alterations in auditory processing and persistent startle hyperreactivity

It is shown that early auditory dysfunction is a conserved consequence of Cntnap2 loss early in development but normalized in adulthood, similar to the Cntnap2 knockout rat model, and reinforces the need to consider sex as a biological variable when investigating neural mechanisms underlying neurodevelopmental disorder...

A P2RX2 exon-2 complex indel disrupts splicing and reduces P2X2 output: implications for DFNA41 and variable expressivity

P2RX2 encodes the ATP-gated P2X2 receptor associated with autosomal dominant non-syndromic hearing loss 41 (DFNA41). DFNA41 is characterized by progressive sensorineural hearing loss and an increased susceptibility to acoustic trauma. However, the specific phenotypic consequences of truncating or splice-altering...

Kcnv2 E151X Mouse Captures Hallmarks of KCNV2-Associated Retinal Dystrophy.

Kcnv2 mutant mice showed markedly reduced photopic responses and reproduced the supernormal rod phenotype described in affected individuals, and this model provides a relevant platform for mechanistic studies and preclinical evaluation of gene-based or pharmacological therapies targeting cone and rod photoreceptor dysf...

Elucidating the role of DEAF1 in neurodevelopment and shared molecular pathways in high-risk autism genes using cortical organoids

This work shows that a DEAF1 mutation in human embryonic stem cells disrupts chromatin accessibility at neuronal gene loci, leading to significant transcriptional alterations, and identifies WNT signaling, TGFβ superfamily signaling, and cell cycle regulation as commonly dysregulated pathways across multiple ASD-associ...