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Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT

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Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT. / Seltzsam, Steve; Wang, Chunyan; Zheng, Bixia; Mann, Nina; Connaughton, Dervla M; Wu, Chen-Han Wilfred; Schneider, Sophia; Schierbaum, Luca; Kause, Franziska; Kolvenbach, Caroline M; Nakayama, Makiko; Dai, Rufeng; Ottlewski, Isabel; Schneider, Ronen; Deutsch, Konstantin; Buerger, Florian; Klämbt, Verena; Mao, Youying; Onuchic-Whitford, Ana C; Nicolas-Frank, Camille; Yousef, Kirollos; Pantel, Dalia; Lai, Ethan W; Salmanullah, Daanya; Majmundar, Amar J; Bauer, Stuart B; Rodig, Nancy M; Somers, Michael J G; Traum, Avram Z; Stein, Deborah R; Daga, Ankana; Baum, Michelle A; Daouk, Ghaleb H; Tasic, Velibor; Awad, Hazem S; Eid, Loai A; El Desoky, Sherif; Shalaby, Mohammed; Kari, Jameela A; Fathy, Hanan M; Soliman, Neveen A; Mane, Shrikant M; Shril, Shirlee; Ferguson, Michael A; Hildebrandt, Friedhelm.

in: GENET MED, Jahrgang 24, Nr. 2, 02.2022, S. 307-318.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Seltzsam, S, Wang, C, Zheng, B, Mann, N, Connaughton, DM, Wu, C-HW, Schneider, S, Schierbaum, L, Kause, F, Kolvenbach, CM, Nakayama, M, Dai, R, Ottlewski, I, Schneider, R, Deutsch, K, Buerger, F, Klämbt, V, Mao, Y, Onuchic-Whitford, AC, Nicolas-Frank, C, Yousef, K, Pantel, D, Lai, EW, Salmanullah, D, Majmundar, AJ, Bauer, SB, Rodig, NM, Somers, MJG, Traum, AZ, Stein, DR, Daga, A, Baum, MA, Daouk, GH, Tasic, V, Awad, HS, Eid, LA, El Desoky, S, Shalaby, M, Kari, JA, Fathy, HM, Soliman, NA, Mane, SM, Shril, S, Ferguson, MA & Hildebrandt, F 2022, 'Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT', GENET MED, Jg. 24, Nr. 2, S. 307-318. https://doi.org/10.1016/j.gim.2021.09.010

APA

Seltzsam, S., Wang, C., Zheng, B., Mann, N., Connaughton, D. M., Wu, C-H. W., Schneider, S., Schierbaum, L., Kause, F., Kolvenbach, C. M., Nakayama, M., Dai, R., Ottlewski, I., Schneider, R., Deutsch, K., Buerger, F., Klämbt, V., Mao, Y., Onuchic-Whitford, A. C., ... Hildebrandt, F. (2022). Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT. GENET MED, 24(2), 307-318. https://doi.org/10.1016/j.gim.2021.09.010

Vancouver

Seltzsam S, Wang C, Zheng B, Mann N, Connaughton DM, Wu C-HW et al. Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT. GENET MED. 2022 Feb;24(2):307-318. https://doi.org/10.1016/j.gim.2021.09.010

Bibtex

@article{bceb26da4ded4111ac3cc9c27db414cb,
title = "Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT",
abstract = "PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES.METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping.RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation.CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.",
keywords = "Alleles, Exome/genetics, Humans, Kidney/abnormalities, Urinary Tract, Urogenital Abnormalities/genetics, Vesico-Ureteral Reflux",
author = "Steve Seltzsam and Chunyan Wang and Bixia Zheng and Nina Mann and Connaughton, {Dervla M} and Wu, {Chen-Han Wilfred} and Sophia Schneider and Luca Schierbaum and Franziska Kause and Kolvenbach, {Caroline M} and Makiko Nakayama and Rufeng Dai and Isabel Ottlewski and Ronen Schneider and Konstantin Deutsch and Florian Buerger and Verena Kl{\"a}mbt and Youying Mao and Onuchic-Whitford, {Ana C} and Camille Nicolas-Frank and Kirollos Yousef and Dalia Pantel and Lai, {Ethan W} and Daanya Salmanullah and Majmundar, {Amar J} and Bauer, {Stuart B} and Rodig, {Nancy M} and Somers, {Michael J G} and Traum, {Avram Z} and Stein, {Deborah R} and Ankana Daga and Baum, {Michelle A} and Daouk, {Ghaleb H} and Velibor Tasic and Awad, {Hazem S} and Eid, {Loai A} and {El Desoky}, Sherif and Mohammed Shalaby and Kari, {Jameela A} and Fathy, {Hanan M} and Soliman, {Neveen A} and Mane, {Shrikant M} and Shirlee Shril and Ferguson, {Michael A} and Friedhelm Hildebrandt",
note = "Copyright {\textcopyright} 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = feb,
doi = "10.1016/j.gim.2021.09.010",
language = "English",
volume = "24",
pages = "307--318",
journal = "GENET MED",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

RIS

TY - JOUR

T1 - Reverse phenotyping facilitates disease allele calling in exome sequencing of patients with CAKUT

AU - Seltzsam, Steve

AU - Wang, Chunyan

AU - Zheng, Bixia

AU - Mann, Nina

AU - Connaughton, Dervla M

AU - Wu, Chen-Han Wilfred

AU - Schneider, Sophia

AU - Schierbaum, Luca

AU - Kause, Franziska

AU - Kolvenbach, Caroline M

AU - Nakayama, Makiko

AU - Dai, Rufeng

AU - Ottlewski, Isabel

AU - Schneider, Ronen

AU - Deutsch, Konstantin

AU - Buerger, Florian

AU - Klämbt, Verena

AU - Mao, Youying

AU - Onuchic-Whitford, Ana C

AU - Nicolas-Frank, Camille

AU - Yousef, Kirollos

AU - Pantel, Dalia

AU - Lai, Ethan W

AU - Salmanullah, Daanya

AU - Majmundar, Amar J

AU - Bauer, Stuart B

AU - Rodig, Nancy M

AU - Somers, Michael J G

AU - Traum, Avram Z

AU - Stein, Deborah R

AU - Daga, Ankana

AU - Baum, Michelle A

AU - Daouk, Ghaleb H

AU - Tasic, Velibor

AU - Awad, Hazem S

AU - Eid, Loai A

AU - El Desoky, Sherif

AU - Shalaby, Mohammed

AU - Kari, Jameela A

AU - Fathy, Hanan M

AU - Soliman, Neveen A

AU - Mane, Shrikant M

AU - Shril, Shirlee

AU - Ferguson, Michael A

AU - Hildebrandt, Friedhelm

N1 - Copyright © 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

PY - 2022/2

Y1 - 2022/2

N2 - PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES.METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping.RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation.CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.

AB - PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) constitute the leading cause of chronic kidney disease in children. In total, 174 monogenic causes of isolated or syndromic CAKUT are known. However, syndromic features may be overlooked when the initial clinical diagnosis of CAKUT is made. We hypothesized that the yield of a molecular genetic diagnosis by exome sequencing (ES) can be increased by applying reverse phenotyping, by re-examining the case for signs/symptoms of the suspected clinical syndrome that results from the genetic variant detected by ES.METHODS: We conducted ES in an international cohort of 731 unrelated families with CAKUT. We evaluated ES data for variants in 174 genes, in which variants are known to cause isolated or syndromic CAKUT. In cases in which ES suggested a previously unreported syndromic phenotype, we conducted reverse phenotyping.RESULTS: In 83 of 731 (11.4%) families, we detected a likely CAKUT-causing genetic variant consistent with an isolated or syndromic CAKUT phenotype. In 19 of these 83 families (22.9%), reverse phenotyping yielded syndromic clinical findings, thereby strengthening the genotype-phenotype correlation.CONCLUSION: We conclude that employing reverse phenotyping in the evaluation of syndromic CAKUT genes by ES provides an important tool to facilitate molecular genetic diagnostics in CAKUT.

KW - Alleles

KW - Exome/genetics

KW - Humans

KW - Kidney/abnormalities

KW - Urinary Tract

KW - Urogenital Abnormalities/genetics

KW - Vesico-Ureteral Reflux

U2 - 10.1016/j.gim.2021.09.010

DO - 10.1016/j.gim.2021.09.010

M3 - SCORING: Journal article

C2 - 34906515

VL - 24

SP - 307

EP - 318

JO - GENET MED

JF - GENET MED

SN - 1098-3600

IS - 2

ER -