The identification of the p.Leu171ArgGIRK2 mutation potentially expands the Keppen-Lubinsky syndrome phenotype to include severe dystonia and ballismus.
Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = -9.30, 95% CI: -17.25 to -1.35, p = 0.02) and OPRM1 rs1799971 (G allele, β = 23.19, 95% CI: 3.27-43.11, p = 0.02); KCNJ6rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI: 1.17-3.71, p = 0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR: 0.69, 95% CI: 0.48-0.99, p = 0.046).
Patients with the COMT G472A-AA genotype (rs4680) and KCNJ6A1032G-A allele (rs2070995) CLBP responded differently to opioid titration, with higher pain intensity requiring higher dosing.
We conclude that mutations in the gene encoding hiGIRK2, a (subunit of) ligand gated potassium channel, is not a major determinant of the susceptibility to NIDDM in Japanese.
Here, we describe a fourth case of a human with a de novo KCNJ6 (GIRK2) mutation, who presented with clinical findings of severe hyperkinetic movement disorder and developmental delay, similar to the Keppen-Lubinsky syndrome but without lipodystrophy.
We sequenced the exomes of three unrelated individuals affected by KPLBS and found de novo heterozygous mutations in KCNJ6 (GIRK2), which encodes an inwardly rectifying potassium channel and maps to the Down syndrome critical region between DIRK1A and DSCR4.
The identification of the p.Leu171ArgGIRK2 mutation potentially expands the Keppen-Lubinsky syndrome phenotype to include severe dystonia and ballismus.
We found that Dp(16)4Yey/+, but not Dp(16)3Yey/+, led to heart defects, suggesting the triplication of the Ifnar1-Kcnj6 region is sufficient to cause DS-associated heart defects.
Our study suggests screening for dominant KCNJ6 mutations in the evaluation of patients with severe movement disorders, which could provide evidence to support a causal role of KCNJ6 in neurological channelopathies.