Taken together, our data suggest the p.D150H mutation is a novel disease-causing mutation in MIP, which leads to congenital progressive cortical punctate cataract by impairing the trafficking mechanism of AQP0.
An arginine to cysteine missense mutation at amino acid 33 (R33C) produced congenital autosomal dominant cataract in a Chinese family for five generations.
This study identified a novel disease-causing mutation p.R187C in MIP in a Chinese cataract family, expanding the mutation spectrum of MIP causing congenital cataract.
Our findings indicate that the genotype TC in polymorphism c.-4T>C and haplotype CCG of rs2269348, c.-4T>C, and rs74641138 in MIP may attach an additional genetic risk factor for ARC in Chinese.
We found significant association between TIMELESS variants and depression with fatigue (D+FAT+) (rs7486220: pointwise P = 0.000099, OR = 1.66; corrected empirical P for the model of D+FAT+ = 0.0056; haplotype 'C-A-A-C' of rs2291739-rs2291738-rs7486220-rs1082214: P = 0.0000075, OR = 1.72) in females, and association to depression with early morning awakening (D+EMA+) (rs1082214: pointwise P = 0.0009, OR = 2.70; corrected empirical P = 0.0374 for the model D+EMA+; haplotype 'G-T' of rs7486220 and rs1082214: P = 0.0001, OR = 3.01) in males.
We obtained supported evidence for involvement of TIMELESS in sleeping problems in an independent set of control individuals with seasonal changes in mood, sleep duration, energy level and social activity in females (P = 0.036, = 0.123 for rs1082214) and with early morning awakening or fatigue in males (P = 0.038 and P = 0.0016, respectively, for rs1082214).
We found significant association between TIMELESS variants and depression with fatigue (D+FAT+) (rs7486220: pointwise P = 0.000099, OR = 1.66; corrected empirical P for the model of D+FAT+ = 0.0056; haplotype 'C-A-A-C' of rs2291739-rs2291738-rs7486220-rs1082214: P = 0.0000075, OR = 1.72) in females, and association to depression with early morning awakening (D+EMA+) (rs1082214: pointwise P = 0.0009, OR = 2.70; corrected empirical P = 0.0374 for the model D+EMA+; haplotype 'G-T' of rs7486220 and rs1082214: P = 0.0001, OR = 3.01) in males.
We obtained supported evidence for involvement of TIMELESS in sleeping problems in an independent set of control individuals with seasonal changes in mood, sleep duration, energy level and social activity in females (P = 0.036, = 0.123 for rs1082214) and with early morning awakening or fatigue in males (P = 0.038 and P = 0.0016, respectively, for rs1082214).
We found significant association between TIMELESS variants and depression with fatigue (D+FAT+) (rs7486220: pointwise P = 0.000099, OR = 1.66; corrected empirical P for the model of D+FAT+ = 0.0056; haplotype 'C-A-A-C' of rs2291739-rs2291738-rs7486220-rs1082214: P = 0.0000075, OR = 1.72) in females, and association to depression with early morning awakening (D+EMA+) (rs1082214: pointwise P = 0.0009, OR = 2.70; corrected empirical P = 0.0374 for the model D+EMA+; haplotype 'G-T' of rs7486220 and rs1082214: P = 0.0001, OR = 3.01) in males.
To establish pathophysiological relevance of cataract formation, the Xenopus laevis oocyte expression system was employed to evaluate functional defects in the mutant proteins, E134G and T138R.
Families with E134G have a uni-lamellar cataract which is stable after birth, whereas families with T138R have multi-focal opacities which increase throughout life.
To establish pathophysiological relevance of cataract formation, the Xenopus laevis oocyte expression system was employed to evaluate functional defects in the mutant proteins, E134G and T138R.
Families with E134G have a uni-lamellar cataract which is stable after birth, whereas families with T138R have multi-focal opacities which increase throughout life.