Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy. / Rudolf, Gabrielle; Lesca, Gaetan; Mehrjouy, Mana M; Labalme, Audrey; Salmi, Manal; Bache, Iben; Bruneau, Nadine; Pendziwiat, Manuela; Fluss, Joel; de Bellescize, Julitta; Scholly, Julia; Moller, Rikke S.; Craiu, Dana; Tommerup, Niels; Valenti-Hirsch, Maria Paola; Schluth-Bolard, Caroline; Sloan-Béna, Frédérique; Helbig, Katherine L; Weckhuysen, Sarah; Edery, Patrick; Coulbaut, Safia; Abbas, Mohamed; Scheffer, Ingrid E; Tang, Sha; Myers, Candace T; Stamberger, Hannah; Carvill, Gemma L; Shinde, Deepali N; Mefford, Heather C; Neagu, Elena; Huether, Robert; Lu, Hsiao-Mei; Dica, Alice; Cohen, Julie S; Iliescu, Catrinel; Pomeran, Cristina; Rubenstein, James; Helbig, Ingo; Sanlaville, Damien; Hirsch, Edouard; Szepetowski, Pierre.
I: European Journal of Human Genetics, Bind 24, Nr. 12, 12.2016, s. 1761-1770.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy
AU - Rudolf, Gabrielle
AU - Lesca, Gaetan
AU - Mehrjouy, Mana M
AU - Labalme, Audrey
AU - Salmi, Manal
AU - Bache, Iben
AU - Bruneau, Nadine
AU - Pendziwiat, Manuela
AU - Fluss, Joel
AU - de Bellescize, Julitta
AU - Scholly, Julia
AU - Moller, Rikke S.
AU - Craiu, Dana
AU - Tommerup, Niels
AU - Valenti-Hirsch, Maria Paola
AU - Schluth-Bolard, Caroline
AU - Sloan-Béna, Frédérique
AU - Helbig, Katherine L
AU - Weckhuysen, Sarah
AU - Edery, Patrick
AU - Coulbaut, Safia
AU - Abbas, Mohamed
AU - Scheffer, Ingrid E
AU - Tang, Sha
AU - Myers, Candace T
AU - Stamberger, Hannah
AU - Carvill, Gemma L
AU - Shinde, Deepali N
AU - Mefford, Heather C
AU - Neagu, Elena
AU - Huether, Robert
AU - Lu, Hsiao-Mei
AU - Dica, Alice
AU - Cohen, Julie S
AU - Iliescu, Catrinel
AU - Pomeran, Cristina
AU - Rubenstein, James
AU - Helbig, Ingo
AU - Sanlaville, Damien
AU - Hirsch, Edouard
AU - Szepetowski, Pierre
PY - 2016/12
Y1 - 2016/12
N2 - Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.
AB - Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.
U2 - 10.1038/ejhg.2016.80
DO - 10.1038/ejhg.2016.80
M3 - Journal article
C2 - 27352968
VL - 24
SP - 1761
EP - 1770
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
SN - 1018-4813
IS - 12
ER -
ID: 171998456