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- W3214900085 abstract "Background Atrial fibrillation (AF) is the most common form of clinical cardiac dysrhythmia responsible for thromboembolic cerebral stroke, congestive heart failure, and death. Aggregating evidence highlights the strong genetic basis of AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of patients, the genetic determinants underpinning AF remain elusive. Methods and Results By genome‐wide screening with polymorphic microsatellite markers and linkage analysis in a 4‐generation Chinese family affected with autosomal‐dominant AF, a novel locus for AF was mapped to chromosome 1q24.2–q25.1, a 3.20‐cM (≈4.19 Mbp) interval between markers D1S2851 and D1S218, with the greatest 2‐point logarithm of odds score of 4.8165 for the marker D1S452 at recombination fraction=0.00. Whole‐exome sequencing and bioinformatics analyses showed that within the mapping region, only the mutation in the paired related homeobox 1 ( PRRX1 ) gene, NM_022716.4:c.319C>T;(p.Gln107*), cosegregated with AF in the family. In addition, sequencing analyses of PRRX1 in another cohort of 225 unrelated patients with AF revealed a new mutation, NM_022716.4:c.437G>T; (p.Arg146Ile), in a patient. The 2 mutations were absent in 908 control subjects. Biological analyses in HeLa cells demonstrated that the 2 mutants had significantly diminished transactivation on the target genes ISL1 and SHOX2 and markedly decreased ability to bind the promoters of ISL1 and SHOX2 (2 genes causally linked to AF), although with normal intracellular distribution. Conclusions This study first indicates that PRRX1 loss‐of‐function mutations predispose to AF, which provides novel insight into the molecular pathogenesis underpinning AF, implying potential implications for precisive prophylaxis and management of AF." @default.
- W3214900085 created "2021-12-06" @default.
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- W3214900085 date "2021-12-07" @default.
- W3214900085 modified "2023-10-17" @default.
- W3214900085 title "PRRX1 Loss‐of‐Function Mutations Underlying Familial Atrial Fibrillation" @default.
- W3214900085 cites W1835886210 @default.
- W3214900085 cites W1949232027 @default.
- W3214900085 cites W1984143972 @default.
- W3214900085 cites W1985382182 @default.
- W3214900085 cites W1988553250 @default.
- W3214900085 cites W2005451662 @default.
- W3214900085 cites W2007043717 @default.
- W3214900085 cites W2038061157 @default.
- W3214900085 cites W2059140331 @default.
- W3214900085 cites W2092389279 @default.
- W3214900085 cites W2113860186 @default.
- W3214900085 cites W2121394112 @default.
- W3214900085 cites W2132505348 @default.
- W3214900085 cites W2147018083 @default.
- W3214900085 cites W2152124063 @default.
- W3214900085 cites W2313203550 @default.
- W3214900085 cites W2337236768 @default.
- W3214900085 cites W2339307237 @default.
- W3214900085 cites W2441688271 @default.
- W3214900085 cites W2761130328 @default.
- W3214900085 cites W2767998629 @default.
- W3214900085 cites W2807295499 @default.
- W3214900085 cites W2807331888 @default.
- W3214900085 cites W2884743521 @default.
- W3214900085 cites W2896057713 @default.
- W3214900085 cites W2897624804 @default.
- W3214900085 cites W2898520203 @default.
- W3214900085 cites W2901369842 @default.
- W3214900085 cites W2901564477 @default.
- W3214900085 cites W2902855927 @default.
- W3214900085 cites W2903835113 @default.
- W3214900085 cites W2905718881 @default.
- W3214900085 cites W2913772219 @default.
- W3214900085 cites W2944236984 @default.
- W3214900085 cites W2951211893 @default.
- W3214900085 cites W2981880239 @default.
- W3214900085 cites W2982905111 @default.
- W3214900085 cites W2984114374 @default.
- W3214900085 cites W2984326971 @default.
- W3214900085 cites W2984438379 @default.
- W3214900085 cites W2993686854 @default.
- W3214900085 cites W2997045662 @default.
- W3214900085 cites W2999156273 @default.
- W3214900085 cites W2999208679 @default.
- W3214900085 cites W3000106820 @default.
- W3214900085 cites W3003494900 @default.
- W3214900085 cites W3003637744 @default.
- W3214900085 cites W3007633823 @default.
- W3214900085 cites W3011855095 @default.
- W3214900085 cites W3014209586 @default.
- W3214900085 cites W3014848658 @default.
- W3214900085 cites W3016608292 @default.
- W3214900085 cites W3026509946 @default.
- W3214900085 cites W3036755425 @default.
- W3214900085 cites W3048040578 @default.
- W3214900085 cites W3049297159 @default.
- W3214900085 cites W3081803256 @default.
- W3214900085 cites W3085600237 @default.
- W3214900085 cites W3090423464 @default.
- W3214900085 cites W3091195045 @default.
- W3214900085 cites W3092391825 @default.
- W3214900085 cites W3092428974 @default.
- W3214900085 cites W3094463747 @default.
- W3214900085 cites W3107321066 @default.
- W3214900085 cites W3118775927 @default.
- W3214900085 cites W3119007671 @default.
- W3214900085 cites W3120157169 @default.
- W3214900085 cites W3120233301 @default.
- W3214900085 cites W3122226502 @default.
- W3214900085 cites W3122396622 @default.
- W3214900085 cites W3134662101 @default.
- W3214900085 cites W3134747804 @default.
- W3214900085 cites W3135459916 @default.
- W3214900085 cites W3136047227 @default.
- W3214900085 cites W3138851518 @default.
- W3214900085 cites W3152812500 @default.
- W3214900085 cites W3156830755 @default.
- W3214900085 cites W3157433307 @default.
- W3214900085 cites W3159291618 @default.
- W3214900085 cites W3164646940 @default.
- W3214900085 cites W3165868284 @default.
- W3214900085 cites W3172262049 @default.
- W3214900085 cites W3186454829 @default.