Biology:OPHN1
 Generic protein structure example |
Oligophrenin-1 is a protein that in humans is encoded by the OPHN1 gene.[1][2][3]
Function
Oligophrenin 1 has 25 exons and encodes a Rho-GTPase-activating protein. The Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis.
The role of OPHN1 in the medial prefrontal cortex in the behavioural responses to stress, and learned helplessness-inducing effect of OPHN1 deletion in parvalbumin interneurons, is of recent research interest.[4][5] It is also involved in regulation in inhibitory interneurons in the olfactory bulb.[6]
Clinical significance
Mutations in this gene are responsible for non-specific X-linked intellectual disability (previously called mental retardation).[3]
OPHN1 syndrome is a rare disorder characterized by intellectual disability and changes in the part of the brain which controls movement and balance (cerebellum). The syndrome mainly affects males. It is characterized by low muscle tone (hypotonia), developmental and cognitive delay, early-onset seizures, abnormal behavior, characteristic facial features (long face, bulging forehead, under eye creases, deep set eyes, and large ears), crossed eyes (strabismus) and inability to coordinate movements.[7] [8] A small cerebellum and large ventricles can be seen on brain imaging (MRI).[7][9][10] Treatment is supportive and includes physical, occupational and speech and language therapy.[11] In 2014 an OPHN1 patient organization and website was formed to support families and promote OPHN1 syndrome research. [12]
OPHN1 syndrome is caused by mutations in the OPHN1 gene, which is located on the X chromosome. Inheritance is X-linked.[7] Some females who carry a mutation in the OPHN1 gene may have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes.[3]
References
- ↑ "Mapping of the X-breakpoint involved in a balanced X;12 translocation in a female with mild mental retardation". European Journal of Human Genetics 5 (2): 105–9. Aug 1997. doi:10.1159/000484743. PMID 9195162.
- ↑ "Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation". Nature 392 (6679): 923–6. April 1998. doi:10.1038/31940. PMID 9582072. Bibcode: 1998Natur.392..923B.
- ↑ 3.0 3.1 3.2 "Entrez Gene: OPHN1 oligophrenin 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4983.
- ↑ "Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex". Neuron 109 (10): 1636–1656.e8. May 2021. doi:10.1016/j.neuron.2021.03.016. PMID 33831348.
- ↑ "Ophn1 regulation of prefrontal inhibition: A mechanism for stress susceptibility in intellectual disability". Neuron 109 (10): 1583–1584. May 2021. doi:10.1016/j.neuron.2021.04.030. PMID 34015262.
- ↑ "Oligophrenin-1 regulates number, morphology and synaptic properties of adult-born inhibitory interneurons in the olfactory bulb". Human Molecular Genetics 25 (23): 5198–5211. December 2016. doi:10.1093/hmg/ddw340. PMID 27742778.
- ↑ 7.0 7.1 7.2 "X-linked disorders with cerebellar dysgenesis". Orphanet Journal of Rare Diseases 6: 24. May 2011. doi:10.1186/1750-1172-6-24. PMID 21569638.
- ↑ "OPHN1". Genetics Home Reference. 2016. https://ghr.nlm.nih.gov/gene/OPHN1#conditions.
- ↑ "X-linked intellectual disability-cerebellar hypoplasia syndrome.". Orphanet. February 2013. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=137831..
- ↑ "Association of syndromic mental retardation with an Xq12q13.1 duplication encompassing the oligophrenin 1 gene". American Journal of Medical Genetics. Part A 146A (13): 1718–24. July 2008. doi:10.1002/ajmg.a.32365. PMID 18512229.
- ↑ "OPHN1 therapies". Oligophrenin-1 Syndrome Foundation. http://ophn1.org/ophn1-therapies.
- ↑ "OPHN1 therapies". Oligophrenin-1 Syndrome Foundation. http://ophn1.org.
Further reading
- "Genes responsible for nonspecific mental retardation". Molecular Genetics and Metabolism 72 (2): 104–8. February 2001. doi:10.1006/mgme.2000.3128. PMID 11161835.
- "Rho proteins, mental retardation and the cellular basis of cognition". Trends in Neurosciences 25 (4): 191–9. April 2002. doi:10.1016/S0166-2236(00)02118-4. PMID 11998687.
- "Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia". Brain 126 (Pt 7): 1537–44. July 2003. doi:10.1093/brain/awg173. PMID 12805098.
- "Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia". European Journal of Human Genetics 7 (5): 541–8. July 1999. doi:10.1038/sj.ejhg.5200320. PMID 10439959.
- "Determination of the gene structure of human oligophrenin-1 and identification of three novel polymorphisms by screening of DNA from 164 patients with non-specific X-linked mental retardation". Annales de Génétique 43 (1): 5–9. 2000. doi:10.1016/S0003-3995(00)00015-0. PMID 10818214.
- "Significant overexpression of oligophrenin-1 in colorectal tumors detected by cDNA microarray analysis". Cancer Letters 172 (1): 67–73. October 2001. doi:10.1016/S0304-3835(01)00625-5. PMID 11595131.
- "Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees". Molecular Biology and Evolution 20 (8): 1281–9. August 2003. doi:10.1093/molbev/msg134. PMID 12777533.
- "Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia". Journal of Medical Genetics 40 (6): 441–6. June 2003. doi:10.1136/jmg.40.6.441. PMID 12807966.
- "Evidence that a major site of expression of the RHO-GTPASE activating protein, oligophrenin-1, is peripheral myelin". Neuroscience 124 (4): 781–7. 2004. doi:10.1016/j.neuroscience.2004.01.007. PMID 15026118.
- "Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia". Neurology 65 (9): 1364–9. November 2005. doi:10.1212/01.wnl.0000182813.94713.ee. PMID 16221952.
This article incorporates public domain material from the National Institutes of Health document "OPHN1 syndrome".
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