The copy number variation landscape of congenital anomalies of the kidney and urinary tract

被引：143

作者：

Verbitsky, Miguel ^{[1
]}

Westland, Rik ^{[1
,2
]}

Perez, Alejandra ^{[1
]}

Kiryluk, Krzysztof ^{[1
]}

Liu, Qingxue ^{[1
]}

Krithivasan, Priya ^{[1
]}

Mitrotti, Adele ^{[1
]}

Fasel, David A. ^{[1
]}

Batourina, Ekaterina ^{[3
]}

Sampson, Matthew G. ^{[4
]}

Bodria, Monica ^{[5
,6
]}

Werth, Max ^{[1
]}

Kao, Charlly ^{[7
,8
]}

Martino, Jeremiah ^{[1
]}

Capone, Valentina P. ^{[1
]}

Vivante, Asaf ^{[9
,10
,11
,12
]}

Shril, Shirlee ^{[9
]}

Kil, Byum Hee ^{[1
]}

Marasa, Maddalena ^{[1
]}

Zhang, Jun Y. ^{[1
]}

Na, Young-Ji ^{[1
]}

Lim, Tze Y. ^{[1
]}

Ahram, Dina ^{[1
]}

Weng, Patricia L. ^{[13
,14
]}

Heinzen, Erin L. ^{[15
]}

Carrea, Alba ^{[5
,6
]}

Piaggio, Giorgio ^{[5
,6
]}

Gesualdo, Loreto ^{[16
]}

Manca, Valeria ^{[17
]}

Masnata, Giuseppe ^{[17
]}

Gigante, Maddalena ^{[16
]}

Cusi, Daniele ^{[18
]}

Izzi, Claudia ^{[19
,20
,21
]}

Scolari, Francesco ^{[22
]}

van Wijk, Joanna A. E. ^{[2
]}

Saraga, Marijan ^{[23
,24
]}

Santoro, Domenico ^{[25
]}

Conti, Giovanni ^{[26
]}

Zamboli, Pasquale ^{[27
]}

White, Hope ^{[1
]}

Drozdz, Dorota ^{[28
]}

Zachwieja, Katarzyna ^{[28
]}

Miklaszewska, Monika ^{[29
]}

Tkaczyk, Marcin ^{[30
]}

Tomczyk, Daria ^{[30
]}

Krakowska, Anna ^{[30
]}

Sikora, Przemyslaw ^{[31
]}

Jarmolinski, Tomasz ^{[32
]}

Borszewska-Kornacka, Maria K. ^{[33
]}

Pawluch, Robert ^{[33
]}

机构：

[1] Columbia Univ, Dept Med, Div Nephrol, New York, NY 10032 USA

[2] Amsterdam UMC, Dept Pediat Nephrol, Amsterdam, Netherlands

[3] Columbia Univ Coll Phys & Surg, Dept Urol, New York, NY 10032 USA

[4] Univ Michigan, Sch Med, Dept Pediat Nephrol, Ann Arbor, MI USA

[5] Ist Giannina Gaslini, Div Nephrol, Dialysis, Transplantat, Genoa, Italy

[6] Ist Giannina Gaslini, Lab Pathophysiol Uremia, Genoa, Italy

[7] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[8] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[9] Harvard Med Sch, Boston Childrens Hosp, Dept Med, Boston, MA USA

[10] Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Pediat Dept B, Tel Hashomer, Israel

[11] Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Pediat Nephrol Unit, Tel Hashomer, Israel

[12] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[13] Univ Calif Los Angeles, Med Ctr, Dept Pediat Nephrol, Los Angeles, CA 90024 USA

[14] Univ Calif Los Angeles, Med Ctr Santa Monica, Los Angeles, CA USA

[15] Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA

[16] Univ Bari, Dept Emergency & Organ Transplantat, Nephrol Sect, Bari, Italy

[17] Azienda Osped Brotzu, Dept Pediat Urol, Cagliari, Italy

[18] Natl Res Council Italy, Bio4dreams Sci Unit, Inst Biomed Technol Milano, Milan, Italy

[19] Spedali Civil Brescia, Dipartimento Ostetr & Ginecol, Brescia, Italy

[20] Spedali Civil Brescia, Div Nefrol ASST 2, Brescia, Italy

[21] Presidio Montichiari, Brescia, Italy

[22] Univ Brescia, Cattedra Nefrol, Div Nefrol 2, Azienda Osped Spedali Civili Brescia Presidio Mon, Brescia, Italy

[23] Univ Hosp Split, Dept Pediat, Split, Croatia

[24] Univ Split, Sch Med, Split, Croatia

[25] Univ Messina, Dipartimento Med Clin & Sperimentale, Messina, Italy

[26] Azienda Osped Univ G Martino, Dept Pediat Nephrol, Messina, Italy

[27] Univ Campania Luigi Vanvitell, Div Nephrol, Naples, Italy

[28] Jagiellonian Univ, Coll Med, Dialysis Unit, Dept Pediat Nephrol & Hypertens, Krakow, Poland

[29] Jagiellonian Univ, Coll Med, Dept Pediat Nephrol, Krakow, Poland

[30] Polish Mothers Mem Hosp, Dept Pediat Immunol & Nephrol, Res Inst, Lodz, Poland

[31] Med Univ Lublin, Dept Pediat Nephrol, Lublin, Poland

[32] Miedzyrzecki Hosp, Childrens Dept, Miedzyrzecz, Poland

[33] Med Univ Silesia, Dept Pediat, Sch Med, Div Dent Zabrze, Katowice, Poland

[34] Med Univ Warsaw, Dept Pediat & Nephrol, Warsaw, Poland

[35] Univ Zielona Gora, Dept Pediat, Zielona Gora, Poland

[36] Our Ladys Childrens Hosp Crumlin, Dept Clin Genet, Dublin, Ireland

[37] Our Ladys Childrens Hosp Crumlin, Natl Childrens Res Ctr, Dublin, Ireland

[38] Natl Childrens Hosp Tallaght, Dublin, Ireland

[39] Univ Coll Dublin, UCD Sch Med, Our Ladys Childrens Hosp Crumlin, Dublin, Ireland

[40] Univ Penn, Dept Pediat, Perelman Sch Med, Childrens Hosp Philadelphia CHOP,Div Nephrol, Philadelphia, PA 19104 USA

[41] Univ Penn, Dept Epidemiol, Perelman Sch Med, Childrens Hosp Philadelphia CHOP,Div Nephrol, Philadelphia, PA 19104 USA

[42] Univ Missouri, Sch Med, Dept Pediat, Div Nephrol,Childrens Mercy Kansas City, Kansas City, MO 64108 USA

[43] Univ Childrens Hosp, Med Fac Skopje, Skopje, North Macedonia

[44] Heidelberg Univ, Univ Clin Gen Visceral & Transplantat Surg, Heidelberg, Germany

[45] Univ Parma, Dept Med & Surg, Parma, Italy

[46] ICNU Nephrol & Urol Dept, Barcelona, Spain

[47] Paris Descartes Univ, Lab Hereditary Kidney Dis, Imagine Inst, Sorbonne Paris Cite,Inserm,UMR 1163, Paris, France

[48] Columbia Univ Coll Phys & Surg, Dept Pediat Urol, 630 W 168th St, New York, NY 10032 USA

[49] Kravis Childrens Hosp, Mt Sinai Med Ctr, New York, NY USA

[50] Univ New Mexico, Childrens Hosp, Div Pediat Nephrol, Albuquerque, NM 87131 USA

来源：

NATURE GENETICS | 2019年 / 51卷 / 01期

基金：

美国国家卫生研究院;

关键词：

RENAL REPLACEMENT THERAPY; CANDIDATE GENES; VITAMIN-A; BRANCHING MORPHOGENESIS; GENOMIC DISORDERS; DIGEORGE-SYNDROME; RARE VARIANTS; MUTATIONS; DISEASE; DELETION;

D O I：

10.1038/s41588-018-0281-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.

引用

页码：117 / +

页数：13

共 50 条

[1] The copy number variation landscape of congenital anomalies of the kidney and urinary tract
Miguel Verbitsky
Rik Westland
Alejandra Perez
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Qingxue Liu
Priya Krithivasan
Adele Mitrotti
David A. Fasel
Ekaterina Batourina
Matthew G. Sampson
Monica Bodria
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Charlly Kao
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[2] Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract
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