KDM6B
Protein-coding gene in humans
From Wikipedia, the free encyclopedia
Lysine demethylase 6B is a protein that in humans is encoded by the KDM6B (JMJD3) gene.[5]
Regulation during differentiation
KDM6B was found to be expressional increased during cardiac and endothelial differentiation of murine embryonic stem cells.[6]
Small molecule inhibition
A small molecule inhibitor (GSK-J1) has been developed to inhibit the jumonji domain of KDM6 histone demethylase family to modulate proinflammatory response in macrophages.[7]
Role in pathology
Mutations of the KDM6B gene may cause neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities, which was first described in 2019 by Stolerman et al.[8]
Standard laboratory exome sequencing can be used to identify the KDM6B gene variant.
Clinical picture
A 2019 study[8] on symptoms from KDM6B variations reported:
- Delays in speech and motor development
- Dysmorphic facial features including coarse features, a prominent forehead, broad mouth, large and prominent ears, a round face, prognathism, and epicanthal fold
- Musculoskeletal features including somewhat widened and thickened hands and fingers, joint hypermobility, clinodactyly of the fifth fingers, and toe syndactyly
- Neuromuscular hypotonia
- Intellectual disability
- Autism spectrum disorder
A further 2023 international study [9] reported on the following clinical features among individuals with (likely) pathogenic KDM6B variants:
| Feature Name | p value | Total % |
|---|---|---|
| Males | 0.50 | 73% |
| Increased birth weight [>2 SD] | 0.33 | 17% |
| Increased weight [>2 SD] | 0.59 | 14% |
| Tall stature [>2 SD] | 1.0 | 8% |
| Macrocephaly [>2 SD] | 1.0 | 26% |
| At least one feature of overgrowth syndrome | 1.0 | 30% |
| Language/speech delay | 0.15 | 94% |
| Motor delay | 1.0 | 89% |
| Intellectual disability | 0.14 | 63% |
| Autism spectrum (ASD) | 0.51 | 61% |
| Behavior problems, non-ASD | 0.70 | 60% |
| Psychotic disorders [≥12 years old] | 1.0 | 20% |
| Seizures | 0.58 | 13% |
| Sleep disturbances | 0.09 | 32% |
| Movement disorder/gait disturbances/hypertonia/ataxia | 0.67 | 24% |
| Hypotonia | 1.0 | 57% |
| Neonatal feeding difficulties or gastroesophageal reflux | 1.0 | 51% |
| Constipation | 1.0 | 18% |
| Congenital heart disease | 0.58 | 13% |
| Cleft lip/palate/uvula | 0.03b | 4% |
| Genitourinary system abnormalities | 1.0 | 10% |
| Joint hypermobility | 1.0 | 42% |
| Scoliosis/kyphosis/lordosis | 0.58 | 13% |
| Syndactyly | 0.15 | 9% |
| Short fingers or toes | 1.0 | 9% |
| Broad fingers/fingertips/hands/toes/feet | 1.0 | 20% |
| Myopia/amblyopia | 0.08 | 33% |
| Strabismus | 0.58 | 13% |
| Hearing loss | 1.0 | 2% |
| Recurrent ear infections | 1.0 | 12% |
Epidemiology
For patients reporting intellectual disability and/or developmental delay, approximately 0.12% have de novo alterations in the KDM6B gene.
Related conditions
Overlapping phenotypic features for patients between KDM6A associated with Kabuki syndrome and KDM6B variations include prominent ears, abnormal dentition, congenital heart disease, feeding difficulties, cryptorchidism, joint hyper-mobility, developmental delay, hypotonia, and behavioral difficulties.
Ongoing research
According to a study published in 2022, pathologic mutations of KDM6B were found in five patients with cerebral folate deficiency.[10]
