OPHN1

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.{{cite journal | vauthors = Wang M, Gallo NB, Tai Y, Li B, Van Aelst L | title = Oligophrenin-1 moderates behavioral responses to stress by regulating parvalbumin interneuron activity in the medial prefrontal cortex | journal = Neuron | volume = 109 | issue = 10 | pages = 1636–1656.e8 | date = May 2021 | pmid = 33831348 | doi = 10.1016/j.neuron.2021.03.016| pmc=8141044 }}{{cite journal | vauthors = Cvetkovska V, Bagot RC | title = Ophn1 regulation of prefrontal inhibition: A mechanism for stress susceptibility in intellectual disability | journal = Neuron | volume = 109 | issue = 10 | pages = 1583–1584 | date = May 2021 | pmid = 34015262 | doi = 10.1016/j.neuron.2021.04.030 | s2cid = 235074402 | doi-access = free }} It is also involved in regulation in inhibitory interneurons in the olfactory bulb.{{cite journal | vauthors = Redolfi N, Galla L, Maset A, Murru L, Savoia E, Zamparo I, Gritti A, Billuart P, Passafaro M, Lodovichi C | display-authors = 6 | title = Oligophrenin-1 regulates number, morphology and synaptic properties of adult-born inhibitory interneurons in the olfactory bulb | journal = Human Molecular Genetics | volume = 25 | issue = 23 | pages = 5198–5211 | date = December 2016 | pmid = 27742778 | doi = 10.1093/hmg/ddw340 | doi-access = free }}

Mutations in this gene are responsible for non-specific X-linked intellectual disability (previously called mental retardation).

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.{{cite journal | vauthors = Zanni G, Bertini ES | title = X-linked disorders with cerebellar dysgenesis | journal = Orphanet Journal of Rare Diseases | volume = 6 | pages = 24 | date = May 2011 | pmid = 21569638 | pmc = 3115841 | doi = 10.1186/1750-1172-6-24 | doi-access = free }}

{{cite journal | title = OPHN1 | journal = Genetics Home Reference | year = 2016 | url = https://ghr.nlm.nih.gov/gene/OPHN1#conditions | access-date = 2018-09-29 | archive-date = 2018-09-29 | archive-url = https://web.archive.org/web/20180929080408/https://ghr.nlm.nih.gov/gene/OPHN1#conditions | url-status = dead }} A small cerebellum and large ventricles can be seen on brain imaging (MRI).{{cite web | vauthors = Zanni G | title = X-linked intellectual disability-cerebellar hypoplasia syndrome. | work = Orphanet | date = February 2013 | url = http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=137831. }}{{cite journal | vauthors = Bedeschi MF, Novelli A, Bernardini L, Parazzini C, Bianchi V, Torres B, Natacci F, Giuffrida MG, Ficarazzi P, Dallapiccola B, Lalatta F | title = Association of syndromic mental retardation with an Xq12q13.1 duplication encompassing the oligophrenin 1 gene | journal = American Journal of Medical Genetics. Part A | volume = 146A | issue = 13 | pages = 1718–24 | date = July 2008 | pmid = 18512229 | doi = 10.1002/ajmg.a.32365 | s2cid = 39448434 }} Treatment is supportive and includes physical, occupational and speech and language therapy.{{cite web | title = OPHN1 therapies | work = Oligophrenin-1 Syndrome Foundation | url = http://ophn1.org/ophn1-therapies }}

In 2014 an OPHN1 patient organization and website was formed to support families and promote OPHN1 syndrome research. {{cite web | title = OPHN1 therapies | work = Oligophrenin-1 Syndrome Foundation | url = http://ophn1.org }}

OPHN1 syndrome is caused by mutations in the OPHN1 gene, which is located on the X chromosome. Inheritance is X-linked. Some females who carry a mutation in the OPHN1 gene may have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes.

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• {{cite journal | vauthors = Castellví-Bel S, Milà M | title = Genes responsible for nonspecific mental retardation | journal = Molecular Genetics and Metabolism | volume = 72 | issue = 2 | pages = 104–8 | date = February 2001 | pmid = 11161835 | doi = 10.1006/mgme.2000.3128 }}
• {{cite journal | vauthors = Ramakers GJ | title = Rho proteins, mental retardation and the cellular basis of cognition | journal = Trends in Neurosciences | volume = 25 | issue = 4 | pages = 191–9 | date = April 2002 | pmid = 11998687 | doi = 10.1016/S0166-2236(00)02118-4 | s2cid = 13941716 }}
• {{cite journal | vauthors = Bergmann C, Zerres K, Senderek J, Rudnik-Schoneborn S, Eggermann T, Häusler M, Mull M, Ramaekers VT | title = Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia | journal = Brain | volume = 126 | issue = Pt 7 | pages = 1537–44 | date = July 2003 | pmid = 12805098 | doi = 10.1093/brain/awg173 | doi-access = free }}
• {{cite journal | vauthors = Tentler D, Gustavsson P, Leisti J, Schueler M, Chelly J, Timonen E, Annerén G, Willard HF, Dahl N | title = Deletion including the oligophrenin-1 gene associated with enlarged cerebral ventricles, cerebellar hypoplasia, seizures and ataxia | journal = European Journal of Human Genetics | volume = 7 | issue = 5 | pages = 541–8 | date = July 1999 | pmid = 10439959 | doi = 10.1038/sj.ejhg.5200320 | doi-access = free }}
• {{cite journal | vauthors = Billuart P, Chelly J, Carrié A, Vinet M, Couvert P, McDonell N, Zemni R, Kahn A, Moraine C, Beldjord C, Bienvenu T | title = 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 | journal = Annales de Génétique | volume = 43 | issue = 1 | pages = 5–9 | year = 2000 | pmid = 10818214 | doi = 10.1016/S0003-3995(00)00015-0 }}
• {{cite journal | vauthors = Pinheiro NA, Caballero OL, Soares F, Reis LF, Simpson AJ | title = Significant overexpression of oligophrenin-1 in colorectal tumors detected by cDNA microarray analysis | journal = Cancer Letters | volume = 172 | issue = 1 | pages = 67–73 | date = October 2001 | pmid = 11595131 | doi = 10.1016/S0304-3835(01)00625-5 }}
• {{cite journal | vauthors = Kitano T, Schwarz C, Nickel B, Pääbo S | title = Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees | journal = Molecular Biology and Evolution | volume = 20 | issue = 8 | pages = 1281–9 | date = August 2003 | pmid = 12777533 | doi = 10.1093/molbev/msg134 | doi-access = free }}
• {{cite journal | vauthors = Philip N, Chabrol B, Lossi AM, Cardoso C, Guerrini R, Dobyns WB, Raybaud C, Villard L | title = Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia | journal = Journal of Medical Genetics | volume = 40 | issue = 6 | pages = 441–6 | date = June 2003 | pmid = 12807966 | pmc = 1735502 | doi = 10.1136/jmg.40.6.441 }}
• {{cite journal | vauthors = Xiao J, Neylon CB, Nicholson GA, Furness JB | title = Evidence that a major site of expression of the RHO-GTPASE activating protein, oligophrenin-1, is peripheral myelin | journal = Neuroscience | volume = 124 | issue = 4 | pages = 781–7 | year = 2004 | pmid = 15026118 | doi = 10.1016/j.neuroscience.2004.01.007 | s2cid = 10045850 }}
• {{cite journal | vauthors = Zanni G, Saillour Y, Nagara M, Billuart P, Castelnau L, Moraine C, Faivre L, Bertini E, Durr A, Guichet A, Rodriguez D, des Portes V, Beldjord C, Chelly J | title = Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia | journal = Neurology | volume = 65 | issue = 9 | pages = 1364–9 | date = November 2005 | pmid = 16221952 | doi = 10.1212/01.wnl.0000182813.94713.ee | s2cid = 21028212 }}

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{{Include-NIH|url=https://rarediseases.info.nih.gov/diseases/13093/ophn1-syndrome|title = OPHN1 syndrome}}

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