BACKGROUND: In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis. METHODS: WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously. RESULTS: Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities. CONCLUSIONS: Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.
BACKGROUND: In the absence of cytogenetic abnormality, fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies show a higher likelihood of monogenic causes; however, defining the underlying pathology can be challenging. Here, we investigate the value of whole-exome sequencing (WES) in fetuses with CAKUT but normal findings upon karyotyping and chromosome microarray analysis. METHODS: WES was performed on DNA from the cord blood of 30 fetuses with unexplained CAKUT with/without other structural anomalies. In the first 23 cases, sequencing was initially performed on fetal DNA only; for the remaining seven cases, the trio of fetus, mother and father was sequenced simultaneously. RESULTS: Of the 30 cases, pathogenic variants were identified in 4 (13%) (UMOD, NEK8, HNF1B and BBS2) and incidental variants in 2 (7%) (HSPD1 and GRIN2B). Furthermore, two of the above four cases had other anomalies in addition to CAKUT. Thus, the detection rate was only 2/22 (9.1%) for isolated CAKUT and 2/8 (25%) for CAKUT with other abnormalities. CONCLUSIONS: Applying WES to the prenatal diagnostic approach in CAKUT fetuses with or without other anomalies allows for an accurate and early etiology-based diagnosis and improved clinical management. To expedite interpretation of the results, trio sequencing should be employed; however, interpretation may nevertheless be compromised by incomplete coverage of all relevant genes.
Authors: Angie C Jelin; Katelynn G Sagaser; Katherine R Forster; Tochi Ibekwe; Mary E Norton; Eric B Jelin Journal: Prenat Diagn Date: 2020-02-19 Impact factor: 3.050
Authors: Elizabeth A Normand; Alicia Braxton; Salma Nassef; Patricia A Ward; Francesco Vetrini; Weimin He; Vipulkumar Patel; Chunjing Qu; Lauren E Westerfield; Samantha Stover; Avinash V Dharmadhikari; Donna M Muzny; Richard A Gibbs; Hongzheng Dai; Linyan Meng; Xia Wang; Rui Xiao; Pengfei Liu; Weimin Bi; Fan Xia; Magdalena Walkiewicz; Ignatia B Van den Veyver; Christine M Eng; Yaping Yang Journal: Genome Med Date: 2018-09-28 Impact factor: 11.117
Authors: Claire E Fishman; Maede Mohebnasab; Jessica van Setten; Francesca Zanoni; Chen Wang; Silvia Deaglio; Antonio Amoroso; Lauren Callans; Teun van Gelder; Sangho Lee; Krzysztof Kiryluk; Matthew B Lanktree; Brendan J Keating Journal: Front Genet Date: 2019-11-15 Impact factor: 4.599