TY - JOUR
T1 - Major brain malformations
T2 - corpus callosum dysgenesis, agenesis of septum pellucidum and polymicrogyria in patients with BCORL1-related disorders
AU - Gafner, Michal
AU - Michelson, Marina
AU - Argilli, Emanuela
AU - Yosovich, Keren
AU - Sherr, Elliott H.
AU - Parks, Kendall C.
AU - England, Eleina M.
AU - Hady-Cohen, Ronen
AU - Leibovitz, Zvi
AU - Lev, Dorit
AU - Michaeli-Yosef, Yael
AU - Lerman-Sagie, Tally
AU - Blumkin, Lubov
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
PY - 2022/2
Y1 - 2022/2
N2 - Objective: BCORL1, a transcriptional co-repressor, has a role in cortical migration, neuronal differentiation, maturation, and cerebellar development. We describe BCORL1 as a new genetic cause for major brain malformations. Methods and results: We report three patients from two unrelated families with neonatal onset intractable epilepsy and profound global developmental delay. Brain MRI of two siblings from the first family depicted hypoplastic corpus callosum and septal agenesis (ASP) in the older brother and unilateral perisylvian polymicrogyria (PMG) in the younger one. MRI of the patient from the second family demonstrated complete agenesis of corpus callosum (CC). Whole Exome Sequencing revealed a novel hemizygous variant in NM_021946.5 (BCORL1):c.796C>T (p.Pro266Ser) in the two siblings from the first family and the NM_021946.5 (BCORL1): c.3376G>A; p.Asp1126Asn variant in the patient from the second family, both variants inherited from healthy mothers. We reviewed the patients’ charts and MRIs and compared the phenotype to the other published BCORL1-related cases. Brain malformations have not been previously described in association with the BCORL1 phenotype. We discuss the potential influence of BCORL1 on brain development. Conclusions: We suggest that BCORL1 variants present with a spectrum of neurodevelopmental disorders and can lead to major brain malformations originating at different stages of fetal development. We suggest adding BCORL1 to the genetic causes of PMG, ASP, and CC dysgenesis.
AB - Objective: BCORL1, a transcriptional co-repressor, has a role in cortical migration, neuronal differentiation, maturation, and cerebellar development. We describe BCORL1 as a new genetic cause for major brain malformations. Methods and results: We report three patients from two unrelated families with neonatal onset intractable epilepsy and profound global developmental delay. Brain MRI of two siblings from the first family depicted hypoplastic corpus callosum and septal agenesis (ASP) in the older brother and unilateral perisylvian polymicrogyria (PMG) in the younger one. MRI of the patient from the second family demonstrated complete agenesis of corpus callosum (CC). Whole Exome Sequencing revealed a novel hemizygous variant in NM_021946.5 (BCORL1):c.796C>T (p.Pro266Ser) in the two siblings from the first family and the NM_021946.5 (BCORL1): c.3376G>A; p.Asp1126Asn variant in the patient from the second family, both variants inherited from healthy mothers. We reviewed the patients’ charts and MRIs and compared the phenotype to the other published BCORL1-related cases. Brain malformations have not been previously described in association with the BCORL1 phenotype. We discuss the potential influence of BCORL1 on brain development. Conclusions: We suggest that BCORL1 variants present with a spectrum of neurodevelopmental disorders and can lead to major brain malformations originating at different stages of fetal development. We suggest adding BCORL1 to the genetic causes of PMG, ASP, and CC dysgenesis.
UR - http://www.scopus.com/inward/record.url?scp=85112717590&partnerID=8YFLogxK
U2 - 10.1038/s10038-021-00971-5
DO - 10.1038/s10038-021-00971-5
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 34400773
AN - SCOPUS:85112717590
SN - 1434-5161
VL - 67
SP - 95
EP - 101
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 2
ER -