首页|RFC2 may contribute to the pathogenicity of Williams syndrome revealed in a zebrafish model

RFC2 may contribute to the pathogenicity of Williams syndrome revealed in a zebrafish model

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Williams syndrome(WS)is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23,characterized by intellectual disability,distinctive craniofacial and dental features,and cardiovascular problems.Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes.Here,we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2,as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2.To investigate the potential involvement of RFC2 in WS pathogenicity,we generate a rfc2 knockout(KO)zebrafish using CRISPR-Cas9 technology.Additionally,we generate a KO zebrafish of its paralog gene,rfc5,to better understand the functions of these RFC genes in development and disease.Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS,including small head and brain,jaw and dental defects,and vascular problems.RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish.In addition,heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion.These results suggest that RFC2 may contribute to the pathogenicity of WS,as evidenced by the zebrafish model.

Williams syndromeRFC2RFC5ZebrafishKnockoutCRISPR-Cas9

Ji-Won Park、Tae-lk Choi、Tae-Yoon Kim、Yu-Ri Lee、Dilan Wellalage Don、Jaya K.George-Abraham、Laurie A.Robak、Cristina C.Trandafir、Pengfei Liu、Jill A.Rosenfeld、Tae Hyeong Kim、Florence Petit、Yoo-Mi Kim、Chong Kun Cheon、Yoonsung Lee、Cheol-Hee Kim

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Department of Biology,Chungnam National University,Daejeon 34134,Republic of Korea

Department of Pediatrics,The University of Texas at Austin Dell Medical School,Austin,TX 78723,USA

Department of Molecular and Human Genetics,Baylor College of Medicine,Houston,TX 77030,USA

Baylor Genetics Laboratories,Houston,TX 77021,USA

Department of Pediatrics,Kyung Hee University Hospital at Gangdong,Seoul 05278,Republic of Korea

Univ.Lille,CHU Lille,Clinique de génétique Guy Fontaine,F-59000 Lille,France

Department of Pediatrics,Chungnam National University Sejong Hospital,Sejong 30099,Republic of Korea

Department of Pediatrics,Pusan National University Children's Hospital,Yangsan 50612,Republic of Korea

Research Institute for Convergence of Biomedical Science and Technology,Pusan National University Yangsan Hospital,Yangsan 50612,Republic of Korea

Clinical Research Institute,Kyung Hee University Hospital at Gangdong,School of Medicine,Kyung Hee University,Seoul 05278,Republic of Korea

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2024

10.1016/j.jgg.2024.09.016

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(12)