Dataset Information
A de novo variant in the X-linked gene CNKSR2 is associated with seizures and mild intellectual disability in a female patient.
Ontology highlight
ABSTRACT: Background
Eight different deletions and point variants of the X-chromosomal gene CNKSR2 have been reported in families with males presenting intellectual disability (ID) and epilepsy. Obligate carrier females with a frameshift variant in the N-terminal protein coding part of CNKSR2 or with a deletion of the complete gene are not affected. Only for one C-terminal nonsense variant, two carrier females were mildly affected by seizures without or with mild motor and language delay.Methods
Exome sequencing was performed in one female child of a Dutch family, presenting seizures, mild ID, facial dysmorphisms, and abnormalities of the extremities. Potential causative variants were validated by Sanger sequencing. X-chromosome-inactivation (XCI) analysis was performed by methylation-sensitive PCR and fragment-length analysis of the androgen-receptor CAG repeat polymorphism.Results
We identified a de novo variant, c.2304G>A (p.(Trp768*)), in the C-terminal protein coding part of the X-chromosomal gene CNKSR2 in a female patient with seizures and mild ID. Sanger sequencing confirmed the presence of this nonsense variant. XCI analysis showed a mild skewing of X inactivation (20:80) in the blood of our patient. Our variant is the second C-terminal-affecting CNKSR2 variant described in neurologically affected females.Conclusion
Our results indicate that CNKSR2 nonsense variants in the C-terminal coding part can result in ID with seizures in female variant carriers.
SUBMITTER: Polla DL
PROVIDER: S-EPMC6785448 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
A de novo variant in the X-linked gene CNKSR2 is associated with seizures and mild intellectual disability in a female patient.
Molecular genetics & genomic medicine 20190815 10
<h4>Background</h4>Eight different deletions and point variants of the X-chromosomal gene CNKSR2 have been reported in families with males presenting intellectual disability (ID) and epilepsy. Obligate carrier females with a frameshift variant in the N-terminal protein coding part of CNKSR2 or with a deletion of the complete gene are not affected. Only for one C-terminal nonsense variant, two carrier females were mildly affected by seizures without or with mild motor and language delay.<h4>Metho ...[more]