Adi Reches1,2,3, Liran Hiersch4,5,6, Sharon Simchoni1, Dalit Barel1, Rotem Greenberg1, Liat Ben Sira3,7, Gustavo Malinger2,3, Yuval Yaron1,2,3. 1. Prenatal Genetic Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel. 2. Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel. 4. Prenatal Genetic Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel. lirhir@gmail.com. 5. Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel. lirhir@gmail.com. 6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel. lirhir@gmail.com. 7. Radiology Department, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel.
Abstract
OBJECTIVE: We describe our experience with whole-exome sequencing (WES) in fetuses with central nervous system (CNS) abnormalities following a normal chromosomal microarray result. METHODS: During the study period (2014-2017) 7 cases (9 fetuses) with prenatally diagnosed CNS abnormality, whose chromosomal microarray analysis was negative, were offered whole-exome sequencing analysis. RESULTS: A pathogenic or a likely pathogenic variant was found in 5 cases including a previously described, likely pathogenic de novo TUBA1A variant (Case #1); a previously described homozygous VRK1 variant (Case #2); an X-linked ARX variant (Case #3); a likely pathogenic heterozygous variant in the TUBB3 gene (Case #5). Finally, in two fetuses of the same couple (Case #6), a compound heterozygous state was detected, consisting of the NPHP1 gene deletion and a sequence variant of uncertain significance. Two additional cases had normal WES results. CONCLUSION: Whole-exome sequencing may improve prenatal diagnosis in fetuses with CNS abnormalities.
OBJECTIVE: We describe our experience with whole-exome sequencing (WES) in fetuses with central nervous system (CNS) abnormalities following a normal chromosomal microarray result. METHODS: During the study period (2014-2017) 7 cases (9 fetuses) with prenatally diagnosed CNS abnormality, whose chromosomal microarray analysis was negative, were offered whole-exome sequencing analysis. RESULTS: A pathogenic or a likely pathogenic variant was found in 5 cases including a previously described, likely pathogenic de novo TUBA1A variant (Case #1); a previously described homozygous VRK1 variant (Case #2); an X-linked ARX variant (Case #3); a likely pathogenic heterozygous variant in the TUBB3 gene (Case #5). Finally, in two fetuses of the same couple (Case #6), a compound heterozygous state was detected, consisting of the NPHP1 gene deletion and a sequence variant of uncertain significance. Two additional cases had normal WES results. CONCLUSION: Whole-exome sequencing may improve prenatal diagnosis in fetuses with CNS abnormalities.
Authors: Maayke A de Koning; Mariëtte J V Hoffer; Esther A R Nibbeling; Emilia K Bijlsma; Menno J P Toirkens; Phebe N Adama-Scheltema; E Joanne Verweij; Marieke B Veenhof; Gijs W E Santen; Cacha M P C D Peeters-Scholte Journal: Clin Genet Date: 2021-10-19 Impact factor: 4.296
Authors: Chloe A Stutterd; Stefanie Brock; Katrien Stouffs; Miriam Fanjul-Fernandez; Paul J Lockhart; George McGillivray; Simone Mandelstam; Kate Pope; Martin B Delatycki; Anna Jansen; Richard J Leventer Journal: Brain Commun Date: 2020-12-26
Authors: Y Yaron; V Ofen Glassner; A Mory; N Zunz Henig; A Kurolap; A Bar Shira; D Brabbing Goldstein; D Marom; L Ben Sira; H Baris Feldman; G Malinger; K Krajden Haratz; A Reches Journal: Ultrasound Obstet Gynecol Date: 2022-07 Impact factor: 8.678