title: Six novel rare non-synonymous mutations for migraine without aura identified by exome sequencing.
abstract: Migraine without aura (MWO) is the most common among migraine group, and is mainly associated with genetic, physical and chemical factors, and hormonal changes. We aimed to identify novel non-synonymous mutations predisposing to the susceptibility to MWO in a Chinese sample using exome sequencing. Four patients with MWO from a family and four non-migraine subjects unrelated with these patients were genotyped using whole-exome sequencing. Bioinformatics analysis was used to screen possible susceptibility gene mutations, which were then verified by PCR. In four patients with MWO, six novel rare non-synonymous mutations were observed, including EDA2R (G170A), UBE2NL (T266G), GBP2 (A907G), EMR1 (C264G), CLCNKB (A1225G), and ARHGAP28 (C413G). It is worth stressing that GBP2 (A907G) was absent in any control subject. Multiple genes predispose to the susceptibility to MWO. ARHGAP28-, EMR1-, and GBP2-encoded proteins may affect angiokinesis, which supports vasogenic theory for the etiological hypothesis of this disease. CLCNKB-encoded protein may affect cell membrane potential, which is consistent with the cortical spreading depression theory. UBE2NL-encoded protein may regulate cellular responses to 5-hydroxytryptamine, which is in accordance with trigeminovascular reflex theory. EDA2R and UBE2NL are located on the X chromosome, which supports that this disease may have gender differences in genetic predisposition. Replication in larger sample size would significantly strengthen these findings.
authors.affiliation: a Department of Neurology , Shanghai First People's Hospital, Shanghai Jiao-Tong University School of Medicine , China and.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a Department of Neurology , Shanghai First People's Hospital, Shanghai Jiao-Tong University School of Medicine , China and.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: a Department of Neurology , Shanghai First People's Hospital, Shanghai Jiao-Tong University School of Medicine , China and.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: a Department of Neurology , Shanghai First People's Hospital, Shanghai Jiao-Tong University School of Medicine , China and.
authors.forename: Zhi-Fei
authors.initials: ZF
authors.lastname: You
authors.affiliation: b Department of Psychiatry , Yale University School of Medicine , New Haven, CT , USA.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.affiliation: a Department of Neurology , Shanghai First People's Hospital, Shanghai Jiao-Tong University School of Medicine , China and.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Wang
mesh_terms: D002135:Calcium-Binding Proteins; D018118:Chloride Channels / Q000235:genetics; D019295:Computational Biology; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D005192:Family Health; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D020326:Migraine without Aura / Q000235:genetics*; D009077:Mucins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics; D053340:Xedar Receptor / Q000235:genetics
chemical_list: C094471:ADGRE1 protein, human; C000603954:ARHGAP28 protein, human; C412733:CLCNKB protein, human; D002135:Calcium-Binding Proteins; D018118:Chloride Channels; C506011:EDA2R protein, human; D020690:GTPase-Activating Proteins; D008562:Membrane Glycoproteins; D009077:Mucins; D043562:Receptors, G-Protein-Coupled; D053340:Xedar Receptor; C471607:UBE2N protein, human; D044763:Ubiquitin-Conjugating Enzymes; C534329:GBP2 protein, human; D019204:GTP-Binding Proteins
keywords: Chinese population; etiological hypothesis; exome sequencing; migraine without aura; non-synonymous mutations; rare variants