Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy
- PMID: 14985377
- PMCID: PMC1735688
- DOI: 10.1136/jmg.2003.013680
Identification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy
Abstract
A four generation family is described in which some men of normal intelligence have epilepsy and others have various combinations of epilepsy, learning difficulties, macrocephaly, and aggressive behaviour. As the phenotype in this family is distinct from other X linked recessive disorders linkage studies were carried out. Linkage analysis was done using X chromosome microsatellite polymorphisms to define the interval containing the causative gene. Genes from within the region were considered possible candidates and one of these, SYN1, was screened for mutations by direct DNA sequencing of amplified products. Microsatellite analysis showed that the region between MAOB (Xp11.3) and DXS1275 (Xq12) segregated with the disease. Two point linkage analysis demonstrated linkage with DXS1039, lod score 4.06 at theta = 0, and DXS991, 3.63 at theta = 0. Candidate gene analysis led to identification of a nonsense mutation in the gene encoding synapsin I that was present in all affected family members and female carriers and was not present in 287 control chromosomes. Synapsin I is a synaptic vesicle associated protein involved in the regulation of synaptogenesis and neurotransmitter release. The SYN1 nonsense mutation that was identified is the likely cause of the phenotype in this family.
Similar articles
-
A novel SYN1 missense mutation in non-syndromic X-linked intellectual disability affects synaptic vesicle life cycle, clustering and mobility.Hum Mol Genet. 2017 Dec 1;26(23):4699-4714. doi: 10.1093/hmg/ddx352. Hum Mol Genet. 2017. PMID: 28973667
-
Nonsense-mediated mRNA decay and loss-of-function of the protein underlie the X-linked epilepsy associated with the W356× mutation in synapsin I.PLoS One. 2013 Jun 20;8(6):e67724. doi: 10.1371/journal.pone.0067724. Print 2013. PLoS One. 2013. PMID: 23818987 Free PMC article.
-
SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function.Hum Mol Genet. 2011 Jun 15;20(12):2297-307. doi: 10.1093/hmg/ddr122. Epub 2011 Mar 25. Hum Mol Genet. 2011. PMID: 21441247
-
Phenotype definition in epilepsy.Epilepsy Behav. 2006 May;8(3):462-76. doi: 10.1016/j.yebeh.2006.01.012. Epub 2006 Feb 23. Epilepsy Behav. 2006. PMID: 16497563 Review.
-
Mutational analysis of the synapsin III gene on chromosome 22q12-q13 in schizophrenia.Psychiatry Res. 2000 Apr 24;94(1):1-7. doi: 10.1016/s0165-1781(00)00123-2. Psychiatry Res. 2000. PMID: 10788672
Cited by
-
X-Linked Epilepsies: A Narrative Review.Int J Mol Sci. 2024 Apr 8;25(7):4110. doi: 10.3390/ijms25074110. Int J Mol Sci. 2024. PMID: 38612920 Free PMC article. Review.
-
SYN1 variant causes X-linked neurodevelopmental disorders: a case report of variable clinical phenotypes in siblings.Front Neurol. 2024 Mar 21;15:1359287. doi: 10.3389/fneur.2024.1359287. eCollection 2024. Front Neurol. 2024. PMID: 38576531 Free PMC article.
-
Synapsin autoantibodies during pregnancy are associated with fetal abnormalities.Brain Behav Immun Health. 2023 Aug 29;33:100678. doi: 10.1016/j.bbih.2023.100678. eCollection 2023 Nov. Brain Behav Immun Health. 2023. PMID: 37692096 Free PMC article.
-
Orchestrating vesicular and nonvesicular membrane dynamics by intrinsically disordered proteins.EMBO Rep. 2023 Nov 6;24(11):e57758. doi: 10.15252/embr.202357758. Epub 2023 Sep 8. EMBO Rep. 2023. PMID: 37680133 Free PMC article. Review.
-
The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes.Int J Mol Sci. 2023 Apr 4;24(7):6758. doi: 10.3390/ijms24076758. Int J Mol Sci. 2023. PMID: 37047730 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials