TY - JOUR
T1 - A single center experience with publicly funded clinical exome sequencing for neurodevelopmental disorders or multiple congenital anomalies
AU - Pode-Shakked, Ben
AU - Barel, Ortal
AU - Singer, Amihood
AU - Regev, Miriam
AU - Poran, Hana
AU - Eliyahu, Aviva
AU - Finezilber, Yael
AU - Segev, Meirav
AU - Berkenstadt, Michal
AU - Yonath, Hagith
AU - Reznik-Wolf, Haike
AU - Gazit, Yael
AU - Chorin, Odelia
AU - Heimer, Gali
AU - Gabis, Lidia V.
AU - Tzadok, Michal
AU - Nissenkorn, Andreea
AU - Bar-Yosef, Omer
AU - Zohar-Dayan, Efrat
AU - Ben-Zeev, Bruria
AU - Mor, Nofar
AU - Kol, Nitzan
AU - Nayshool, Omri
AU - Shimshoviz, Noam
AU - Bar-Joseph, Ifat
AU - Marek-Yagel, Dina
AU - Javasky, Elisheva
AU - Einy, Reviva
AU - Gal, Moran
AU - Grinshpun-Cohen, Julia
AU - Shohat, Mordechai
AU - Dominissini, Dan
AU - Raas-Rothschild, Annick
AU - Rechavi, Gideon
AU - Pras, Elon
AU - Greenbaum, Lior
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.
AB - Exome sequencing (ES) is an important diagnostic tool for individuals with neurodevelopmental disorders (NDD) and/or multiple congenital anomalies (MCA). However, the cost of ES limits the test's accessibility for many patients. We evaluated the yield of publicly funded clinical ES, performed at a tertiary center in Israel, over a 3-year period (2018–2020). Probands presented with (1) moderate-to-profound global developmental delay (GDD)/intellectual disability (ID); or (2) mild GDD/ID with epilepsy or congenital anomaly; and/or (3) MCA. Subjects with normal chromosomal microarray analysis who met inclusion criteria were included, totaling 280 consecutive cases. Trio ES (proband and parents) was the default option. In 252 cases (90.0%), indication of NDD was noted. Most probands were males (62.9%), and their mean age at ES submission was 9.3 years (range 1 month to 51 years). Molecular diagnosis was reached in 109 probands (38.9%), mainly due to de novo variants (91/109, 83.5%). Disease-causing variants were identified in 92 genes, 15 of which were implicated in more than a single case. Male sex, families with multiple-affected members and premature birth were significantly associated with lower ES yield (p < 0.05). Other factors, including MCA and coexistence of epilepsy, autism spectrum disorder, microcephaly or abnormal brain magnetic resonance imaging findings, were not associated with the yield. To conclude, our findings support the utility of clinical ES in a real-world setting, as part of a publicly funded genetic workup for individuals with GDD/ID and/or MCA.
UR - http://www.scopus.com/inward/record.url?scp=85115770812&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-98646-w
DO - 10.1038/s41598-021-98646-w
M3 - Article
C2 - 34580403
AN - SCOPUS:85115770812
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 19099
ER -