Homozygous missense mutation in STYXL1 associated with moderate intellectual disability, epilepsy and behavioural complexities.
The introduction of massive parallel sequencing has led to the identification of multiple novel genes for intellectual disability (ID) as well as epilepsy. Whereas dominant de novo mutations have been proven to be a leading cause for these disorders, they do not apply to families suggestive of an autosomal recessive inheritance pattern. In this study, we combined the use of linkage analysis with exome sequencing to elucidate the cause of moderate non-syndromic ID, epilepsy and behavioural problems in a consanguineous Asian family. A founder missense mutation was identified in STYXL1. We propose this as a novel candidate gene involved in ID, accompanied by seizures and behavioural problems. Our findings further confirm the genetic heterogeneity of cognitive disorders and genetic epilepsy.
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Laboratory for the Genetics of Cognition, KU Leuven, Leuven, Belgium.
Mala
M
Isrie
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Masoud
M
Zamani Esteki
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Hilde
H
Peeters
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Thierry
T
Voet
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Jeroen
J
Van Houdt
Department of Neurology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
Wim
W
Van Paesschen
Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Laboratory for the Genetics of Cognition, KU Leuven, Leuven, Belgium. Electronic address: Hilde.VanEsch@uzleuven.be.
Hilde
H
Van Esch
D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D044466:Asian People; D001483:Base Sequence; D004827:Epilepsy / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D000066553:Problem Behavior / Q000523:psychology*; D017422:Sequence Analysis, DNA
D051017:Apoptosis Regulatory Proteins; C558168:STYXL1 protein, human
Consanguineous; Exome sequencing; Linkage; STYXL1