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Normal Function
The EXOSC3 gene provides instructions for making a protein known as exosome component 3. As its name suggests, this protein forms one part (subunit) of a large, multi-protein complex known as the RNA exosome. Within cells, this complex helps to process multiple types of RNA, which are chemical cousins of DNA, by cutting (cleaving) RNA molecules in certain places. The RNA exosome also breaks down (degrades) molecules of RNA when they are no longer needed. Appropriate processing and breakdown of RNA molecules is essential for the normal functioning of all cells.
Studies suggest that the activity of exosome component 3 is necessary for the normal development and growth of certain areas of the brain, particularly the cerebellum, which is the part of the brain that coordinates movement. Exosome component 3 also appears to be important for the survival of specialized nerve cells in the spinal cord called motor neurons, which play an essential role in muscle movement.
Health Conditions Related to Genetic Changes
Pontocerebellar hypoplasia
At least 16 mutations in the EXOSC3 gene have been identified in people with a disorder of brain development called pontocerebellar hypoplasia. The major features of this condition include delayed development overall, an unusually small head size (microcephaly), and intellectual disability. EXOSC3 gene mutations cause about half of all cases of a form of the disorder designated pontocerebellar hypoplasia type 1 (PCH1). When PCH1 results from EXOSC3 gene mutations, it is sometimes categorized more specifically as PCH1B. In addition to the features listed above, PCH1B causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord.
The EXOSC3 gene mutations that cause PCH1B result in an exosome component 3 protein with reduced or no function. The most common mutation alters a single protein building block (amino acid) in exosome component 3; it replaces the amino acid aspartic acid with the amino acid alanine at protein position 132 (written as Asp132Ala or D132A). People with this mutation tend to have somewhat less severe brain abnormalities than people with other EXOSC3 gene mutations. Changes in this gene likely impair the activity of the RNA exosome, but it is unclear how these alterations lead to the problems with brain development and loss of motor neurons characteristic of PCH1B.
More About This Health ConditionOther Names for This Gene
- bA3J10.7
- CGI-102
- exosome complex component RRP40
- exosome complex exonuclease RRP40
- hRrp-40
- hRrp40p
- p10
- PCH1B
- ribosomal RNA-processing protein 40
- RRP40
- Rrp40p
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Baas F, van Dijk T. EXOSC3 Pontocerebellar Hypoplasia. 2014 Aug 21 [updated 2020 Sep 24]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK236968/ Citation on PubMed
- Biancheri R, Cassandrini D, Pinto F, Trovato R, Di Rocco M, Mirabelli-Badenier M, Pedemonte M, Panicucci C, Trucks H, Sander T, Zara F, Rossi A, Striano P, Minetti C, Santorelli FM. EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement. J Neurol. 2013 Jul;260(7):1866-70. doi: 10.1007/s00415-013-6896-0. Epub 2013 Apr 7. Citation on PubMed
- Eggens VR, Barth PG, Niermeijer JM, Berg JN, Darin N, Dixit A, Fluss J, Foulds N, Fowler D, Hortobagyi T, Jacques T, King MD, Makrythanasis P, Mate A, Nicoll JA, O'Rourke D, Price S, Williams AN, Wilson L, Suri M, Sztriha L, Dijns-de Wissel MB, van Meegen MT, van Ruissen F, Aronica E, Troost D, Majoie CB, Marquering HA, Poll-The BT, Baas F. EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. Orphanet J Rare Dis. 2014 Feb 13;9:23. doi: 10.1186/1750-1172-9-23. Citation on PubMed or Free article on PubMed Central
- Rudnik-Schoneborn S, Senderek J, Jen JC, Houge G, Seeman P, Puchmajerova A, Graul-Neumann L, Seidel U, Korinthenberg R, Kirschner J, Seeger J, Ryan MM, Muntoni F, Steinlin M, Sztriha L, Colomer J, Hubner C, Brockmann K, Van Maldergem L, Schiff M, Holzinger A, Barth P, Reardon W, Yourshaw M, Nelson SF, Eggermann T, Zerres K. Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. Neurology. 2013 Jan 29;80(5):438-46. doi: 10.1212/WNL.0b013e31827f0f66. Epub 2013 Jan 2. Citation on PubMed or Free article on PubMed Central
- Wan J, Yourshaw M, Mamsa H, Rudnik-Schoneborn S, Menezes MP, Hong JE, Leong DW, Senderek J, Salman MS, Chitayat D, Seeman P, von Moers A, Graul-Neumann L, Kornberg AJ, Castro-Gago M, Sobrido MJ, Sanefuji M, Shieh PB, Salamon N, Kim RC, Vinters HV, Chen Z, Zerres K, Ryan MM, Nelson SF, Jen JC. Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nat Genet. 2012 Apr 29;44(6):704-8. doi: 10.1038/ng.2254. Citation on PubMed or Free article on PubMed Central
- Zanni G, Scotton C, Passarelli C, Fang M, Barresi S, Dallapiccola B, Wu B, Gualandi F, Ferlini A, Bertini E, Wei W. Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. Neurogenetics. 2013 Nov;14(3-4):247-50. doi: 10.1007/s10048-013-0371-z. Epub 2013 Aug 24. Citation on PubMed
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