What is SETBP1?
The SETBP1 gene is located on the long (q) arm of chromosome 18 at position 12.3. This gene contains the instructions to produce SETBP1 protein. The protein is shown to be active in numerous tissues, predominantly in the brain. This suggests that changes involving this gene may impact the development and/or function of brain cells. SETBP1 is a DNA-binding protein that forms part of a group of proteins that act together on histone methylation to make chromatin more accessible and regulate gene expression. There is still more to learn about the overall function of the SETBP1 protein — more research is necessary. DNA changes that lead to a decreased amount of the SETBP1 protein are associated with SETBP1 haploinsufficiency disorder.
Image provided by NCBI
SETBP1 haploinsufficiency disorder
SETBP1 haploinsufficiency disorder, also known as SETBP1 disorder or SETBP1-HD, is a very rare disorder caused by a loss-of-function mutation in one of the two copies of the SETBP1 gene. The one copy of the SETBP1 gene does not produce a sufficient amount of SETBP1 protein for the body to function normally. Individuals with a full or a partial deletion of chromosome 18q12.3 may also have SETBP1-HD. Those reporting a loss-of-function of the SETBP1 gene are reported as de novo. De novo mutations are spontaneous mutations and occur where the family has no history of the disorder. We still do not know the full function of the SETBP1 gene or why a loss of SETBP1 genetic material causes a genetic disease. Individuals with SETBP1-HD are expressive speech impaired and have mild-moderate developmental delay.
The symptoms vary for those impacted by SETBP1-HD. Not all individuals impacted by a loss-of-function of the SETBP1 gene will exhibit all the symptoms. Reported Symptoms:
- speech language difficulties ranging from absent speech to apraxia to expressive language delay
- intellectual disability – ranging from mild to severe
- autistic-like traits
- autism spectrum disorder (ASD)
- Attention deficit hyperactivity disorder (ADHD)
- low muscle tone, hypotonia
- seizures or EEG abnormalities
- delayed motor skills
- decreased fine motor skills
- behavior challenges
- sensory processing differences
- sleep problems
- learning disabilities (dyslexia, dysgraphia, dyscalculia)
- vision problems, often require glasses
- subtle facial differences including a long chin, longer face, dolichocephaly, brachycephaly, downslanting palpebral fissures, thin upper lip, etc.
Check out the SETBP1 haploinsufficiency disorder guide
Listen to Dr Siddharth Srivastava, a pediatric neurologist from Boston Children’s Hospital, talk about the features of SETBP1-HD:
Hear Dr Angela Morgan, a speech pathologist and speech scientist from the Murdoch Children’s Research Institute, talk about the speech and language differences for individuals with SETBP1-HD:
View Dr Angela Morgan’s SETBP1 Speech and Language Study.
SETBP1 haploinsufficiency disorder (SETBP-HD) is also known as SETBP1 disorder, SETBP1-related disorder; SETBP1-related intellectual disability; SETBP1-related developmental delay; Autosomal dominant mental retardation 29 (MRD 29)
Schinzel-Giedion Syndrome (SGS)
A different type of mutation within SETBP1 results in an overproduction or accumulation of SETBP1 protein. The mutation typically lies in or around a hotspot region. These gain-of-function or dominant-negative mutations cause a different disorder called Schinzel-Giedion syndrome (SGS). Schinzel-Giedion syndrome is a severe multi-organ disorder characterized by distinct facial features, neurodevelopmental and structural anomalies. For more information about SGS or to connect with other families impacted by SGS, you can reach out to the Schinzel-Giedion Syndrome Foundation.