A recurrent de novo CUX2 missense variant associated with intellectual disability, seizures, and autism spectrum disorder

TY - JOUR

T1 - A recurrent de novo CUX2 missense variant associated with intellectual disability, seizures, and autism spectrum disorder

AU - Barington, Maria

AU - Risom, Lotte

AU - Ek, Jakob

AU - Uldall, Peter

AU - Ostergaard, Elsebet

PY - 2018/9/1

Y1 - 2018/9/1

N2 - In most patients with intellectual disability (ID), the etiology is unknown, but lately several de novo variants have been associated with ID. One of the involved genes, CUX2, has twice been reported to be affected by a de novo variant c.1768G>A; p.(Glu590Lys) in patients with ID or epileptic encephalopathy. CUX2 is expressed primarily in nervous tissues where it may act as a transcription factor involved in neural specification. Here we describe a third case who was diagnosed with epilepsy including general and myoclonic seizures, moderate to severe cognitive disability, and infantile autism. The patient was heterozygous for the c.1768G>A; p.(Glu590Lys) variant in CUX2 identified by whole exome sequencing. These findings strongly suggest a causal impact of this variant and add to our understanding of a subset of patients with ID, seizures, and autism spectrum disorder as well as suggest an important role for the CUX2 gene in human brain function.

AB - In most patients with intellectual disability (ID), the etiology is unknown, but lately several de novo variants have been associated with ID. One of the involved genes, CUX2, has twice been reported to be affected by a de novo variant c.1768G>A; p.(Glu590Lys) in patients with ID or epileptic encephalopathy. CUX2 is expressed primarily in nervous tissues where it may act as a transcription factor involved in neural specification. Here we describe a third case who was diagnosed with epilepsy including general and myoclonic seizures, moderate to severe cognitive disability, and infantile autism. The patient was heterozygous for the c.1768G>A; p.(Glu590Lys) variant in CUX2 identified by whole exome sequencing. These findings strongly suggest a causal impact of this variant and add to our understanding of a subset of patients with ID, seizures, and autism spectrum disorder as well as suggest an important role for the CUX2 gene in human brain function.

KW - Adolescent

KW - Autism Spectrum Disorder/genetics

KW - Child

KW - Female

KW - Homeodomain Proteins/genetics

KW - Humans

KW - Intellectual Disability/genetics

KW - Male

KW - Mutation, Missense

KW - Seizures/genetics

KW - Syndrome

U2 - 10.1038/s41431-018-0184-5

DO - 10.1038/s41431-018-0184-5

M3 - Journal article

C2 - 29795476

SN - 1018-4813

VL - 26

SP - 1388

EP - 1391

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

IS - 9

ER -