Association between genetic variation of CACNA1H and childhood absence epilepsy.
Extended spectrum of idiopathic generalized epilepsies associated with CACNA1H functional variants.
Reportedly, the variant found in the CACNA1H gene could also contribute the proband's phenotype; however, the variant is a known single nucleotide polymorphism that was considered a risk factor for generalized epilepsy but not the dyskinesia phenotype (5).
Annotations, frequency, and bioinformatic prediction scores of variants in select candidate genes Gene KCNMA1 CACNA1H Position [hg19] 10:78846314 16:1252303 Nukleotit change c.1372C>T c.1853C>T Protein change p.Arg458Ter p.Pro618Leu Zygosity Hom Het EXAC frequency - 0.001201 PhyloP score 2.672 4.985 PhyloP prediction Conserved Conserved SIFT score - (0.01) SIFT prediction - Deleterious Polyphen2 score - (0.991) PolyPhen prediction - Probably damaging Mutation taster score 1 0.999 Mutation taster prediction Disease causing Disease causing dbSNP ID - rs60734921 Read depth 170 47 Transkript NM 001161353 NM 021098.2 Exon 11/28 9/35
In the current study, we detected the mRNA of the three isoforms of the T-type calcium channel CACNA1G (T-type [Ca.sup.2+] channel, Cav3.1), CACNA1H
(T-type [Ca.sup.2+] channel, Cav3.2), and CACNA1I (T-type [Ca.sup.2+] channel, Cav3.3).
Expression of Cacna1d (3-fold), Cacna1g, Cacna1h (4-fold), Cacna2d1, Cacna2d3, and Cacng4 (3-fold) were downregulated in GK compared to control SAN.
Regarding the changes in mRNA of particular interest were (i) downregulation of Gja5 and Gjd3 (4-fold), (ii) downregulation of Trpc6 (6-fold), (iii) downregulation of Hcn4 (5-fold), (iv) downregulation of Cacna1d (3-fold), Cacna1h (4-fold), and Cacng4 (3-fold), (v) downregulation of Kcna5 (5-fold) and Kcnk1 (7-fold) in GK compared to control SAN, and (vi) upregulation of Nppb in GK compared to control SAN.
Bidirectional Sanger sequencing was performed for targeted mutation detection in the KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, and PRKACA genes using DNA extracted from the tumor tissues of the 22 A/CPA patients.
Further, no ATP1A1, ATP2B3, CACNA1D, or CACNA1H mutations were detected.
hsa_AACTTT PRSS12, PPP2CB, CACNA1H
, CTBP2, MORF4L2, et al.
Agnew, "A profile of alternative RNA splicing and transcript variation of CACNA1H
, a human T-channel gene candidate for idiopathic generalized epilepsies," Human Molecular Genetics, vol.
Mendelian forms of hypertension and germline mutations causing early-onset hypertension have highlighted biological pathways that involve renal salt handling (WNK1, WNK4, KLHL3, and CUL3), ion transport (CACNA1D, CACNA1H
, KCNJ5, SCNN1B, and SCNN1G), corticosteroidogenesis (CYP11B2, HSD11B2, NR3C2, CYP11B1, and CYP17A1), and vascular tone (PDE3A) to regulate blood [41-44].