Association Analysis ofNALCNPolymorphisms rs1338041 and rs61973742 in a Chinese Population with Isolated Cervical Dystonia

Abstract

Background. A genome-wide association study (GWAS) demonstrated a possible association between cervical dystonia (CD) and a sodium leak channel, nonselective (NALCN) gene. However, the association between NALCN and CD was largely unknown in Asian population. The present study was carried out to examine the associations between the two single nucleotide polymorphisms (SNPs) rs1338041 and rs61973742 in the NALCN gene and CD in a Chinese population. Methods. In a cohort of 201 patients with isolated CD, we genotyped the two SNPs rs1338041 and rs61973742 using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). We also included 289 unrelated, age- and sex-matched healthy controls (HCs) from the same region. Result. No significant differences were observed in either the genotype distributions or the minor allele frequencies (MAFs) of the two SNPs between the CD patients and the HCs. There were no significant differences between early-onset and late-onset CD patients, between patients with and without a positive family history of dystonia, or between patients with and without tremor or sensory tricks. Conclusion. Lack of association between the SNPs of NALCN and CD suggests that the SNPs of NALCN do not play a role in CD in a Chinese population.

Risk Factor Genes in Patients with Dystonia: A Comprehensive Review

“…The most statistically significant variants were NALCN (rs61973742, rs1338051, rs9518385, rs9518384, rs1338041 rs3916908), COL4A1 (rs619152), RGL1 (rs12132318), OR4X2 3 (rs67863238), intergenic (rs1249277, rs1249281, rs9416795), KIAA1715 (rs10930717), OR4B1 (rs35875350) 118. However, a replication of this GWAS case–control study did not report any association of NALCN , OR4X2 , COL4A1 , and intergenic variants,122 and the results for NALC (rs1338041, rs61973742) were also not reproduced in a Chinese population 123. NALCN is a voltage-independent and cation-non-selective channel.…”

Pathogenic convergence of CNVs in genes functionally associated to a severe neuromotor developmental delay syndrome

“…Protein involved in signaling at neuronal synaptic junctions [ 41 , 42 ] Epileptic encephalopathy [ 43 ] NALCN (611549) 13q33.1 Sodium Leak Channel, Non-Selective Voltage-gated Na + and Ca 2+ channels regulating the resting membrane potential and excitability of neurons [ 44 – 46 ] NALCN deficiency is associated to channelopathies [ 47 ]. NALCN pathogenic variants associated to Neuroaxonal Dystrophy (INAD) patients, severe hypotonia, speech impairment, cognitive delay, epilepsy and mental disability [ 44 , 45 , 48 , 49 ] NALCN associated to dystonia [ 46 , 50 ] RYR3 (180903) 15q14 Ryanodine Receptor 3 Presynaptic endoplasmic reticulum ryanodine receptor-mediated Ca 2+ release [ 51 , 52 ]. Involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules Regulates composition of the protein complex that forms a voltage-independent, nonselective, non-inactivating cation channel permeable to Na + , K + , and Ca 2+ , which regulates the neuronal background sodium leak conductance [ 53 ] RYR3 haploinsuficiency cooperates SCN1A , implicated in epileps y[ 54 , 55 ].…”

Risk Factor Genes in Patients with Dystonia: A Comprehensive Review.

“… 118 However, a replication of this GWAS case–control study did not report any association of NALCN , OR4X2 , COL4A1 , and intergenic variants, 122 and the results for NALC (rs1338041, rs61973742) were also not reproduced in a Chinese population. 123 NALCN is a voltage-independent and cation-non-selective channel. Its main function is the leaky sodium transport across neuronal membranes and the regulation of neuronal excitability.…”