Exome sequencing identifies a likely causative variant in 53%of families with ciliopathy-related features on renal ultrasound after excluding NPHP1 deletions  

作　　者：Konstantin Deutsch Verena Klambt Thomas M.Kitzler Tilman Jobst-Schwan Ronen Schneider Florian Buerger Steve Seltzsam Sherif El Desoky Jameela A.Kari Farkhanda Hafeez Maria Szczepanska Loai A.Eid Hazem S.Awad Muna Al-Saffar Neveen A.Soliman Velibor Tasic Camille Nicolas-Frank Kirollos Yousef Luca M.Schierbaum Sophia Schneider Abdul Halawi Izzeldin Elmubarak Katharina Lemberg Shirlee Shril Shrikant M.Mane Nancy Rodig Friedhelm Hildebrandt 

机构地区：[1]Division of Nephrology,Department of Pediatrics,Boston Children’s Hospital,Harvard Medical School,Boston,MA 02215,USA [2]Department of Pediatric Gastroenterology,Nephrology and Metabolic Diseases,Charite Universitatsmedizin Berlin,Berlin 13353,Germany [3]Berlin Institute of Health at Charitee Universitatsmedizin Berlin,BIH Biomedical Innovation Academy,BIH Charite Clinician Scientist Program,Berlin 10178,Germany [4]Department of Nephrology and Hypertension,FriedrichAlexander-Universitat Erlangen-Nurnberg,Erlangen 91054,Germany [5]Department of Pediatrics,Faculty of Medicine King Abdulaziz University,Pediatric Nephrology Center of Excellence,King Abdulaziz University Hospital,Jeddah 21589,Saudi Arabia [6]Department of Pediatric Nephrology,The Children’s Hospital and Institute of Child Health,Lahore 54000,Pakistan [7]Department of Pediatrics,Faculty of Medical Sciences in Zabrze,Medical University of Silesia in Katowice,Katowice 40-752,Poland [8]Dubai Hospital and Al-Jalila Children’s Specialty Hospital,Kidney Center of Excellence,Dubai 4545,United Arab Emirates [9]Department of Genetics and Genomics,UAE University,Abu Dhabi 15551,United Arab Emirates [10]Department of Pediatrics,Division of Genetics and Genomics,Boston Children’s Hospital,Harvard Medical School,Boston,MA 02215,USA [11]Department of Pediatrics,Center of Pediatric Nephrology and Transplantation,Kasr Al Ainy School of Medicine,Cairo University,Cairo 11562,Egypt [12]Egypt Center for Research and Regenerative Medicine(ECRRM),Cairo 11511,Egypt [13]Medical Faculty Skopje,University Children’s Hospital,Skopje 1000,North Macedonia [14]Department of Genetics,Yale University School of Medicine,New Haven,CT 06520,USA

出　　处：《Genes & Diseases》2024年第5期40-43,共4页基因与疾病（英文）

基　　金：The Deutsche Forschungsgemeinschaft funded V.K.(No.403877094);S.Se(No.442070894)and T.J.S.(No.281319475);V.K.was also funded by the Else-Kroner Fresenius Stiftung(Memorial Grant);the BIH ChariteClinician Scientist Program by the Charite´e Universitatsmedizin Berlin,and the Berlin Institute of Health at Charite.S.Se.was supported by the Deutsche Forschungsgemeinschaft(German Research Foundation)lT.M.K.was also supported by a Post-Doctoral Fellowship award from the KRESCENT Program,a national kidney research training partnership of the Kidney Foundation of Canada,the Canadian Society of Nephrology,and the Canadian Institutes of Health Research.T.J.-S.received funding from the IZKF Erlangen(J70)and the Eva Luise und Horst Kohler Stiftung/Else Kroer-Fresenius Stiftung(RECORD program).

摘　　要：Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common cause.Ciliopathy genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic fibrosis.Patients are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.

关 键 词：DEGENERATION URINARY LIKELY 

分 类 号：R692[医药卫生—泌尿科学]