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Autism-epilepsy phenotype with macrocephaly suggests PTEN, but not GLIALCAM, genetic screening.
- Source :
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BMC medical genetics [BMC Med Genet] 2014 Feb 27; Vol. 15, pp. 26. Date of Electronic Publication: 2014 Feb 27. - Publication Year :
- 2014
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Abstract
- Background: With a complex and extremely high clinical and genetic heterogeneity, autism spectrum disorders (ASD) are better dissected if one takes into account specific endophenotypes. Comorbidity of ASD with epilepsy (or paroxysmal EEG) has long been described and seems to have strong genetic background. Macrocephaly also represents a well-known endophenotype in subgroups of ASD individuals, which suggests pathogenic mechanisms accelerating brain growth in early development and predisposing to the disorder. We attempted to estimate the association of gene variants with neurodevelopmental disorders in patients with autism-epilepsy phenotype (AEP) and cranial overgrowth, analyzing two genes previously reported to be associated with autism and macrocephaly.<br />Methods: We analyzed the coding sequences and exon-intron boundaries of GLIALCAM, encoding an IgG-like cell adhesion protein, in 81 individuals with Autism Spectrum Disorders, either with or without comorbid epilepsy, paroxysmal EEG and/or macrocephaly, and the PTEN gene in the subsample with macrocephaly.<br />Results: Among 81 individuals with ASD, 31 had concurrent macrocephaly. Head circumference, moreover, was over the 99.7th percentile ("extreme" macrocephaly) in 6/31 (19%) patients. Whilst we detected in GLIALCAM several single nucleotide variants without clear pathogenic effects, we found a novel PTEN heterozygous frameshift mutation in one case with "extreme" macrocephaly, autism, intellectual disability and seizures.<br />Conclusions: We did not find a clear association between GLIALCAM mutations and AEP-macrocephaly comorbidity. The identification of a novel frameshift variant of PTEN in a patient with "extreme" macrocephaly, autism, intellectual disability and seizures, confirms this gene as a major candidate in the ASD-macrocephaly endophenotype. The concurrence of epilepsy in the same patient also suggests that PTEN, and the downstream signaling pathway, might deserve to be investigated in autism-epilepsy comorbidity. Working on clinical endophenotypes might be of help to address genetic studies and establish actual causative correlations in autism-epilepsy.
- Subjects :
- Adolescent
Amino Acid Sequence
Base Sequence
Cell Cycle Proteins
Child
Child, Preschool
DNA Mutational Analysis
Female
Frameshift Mutation
Genetic Association Studies
Genetic Predisposition to Disease
Genetic Testing
Humans
Male
Molecular Sequence Data
Young Adult
Abnormalities, Multiple genetics
Autistic Disorder genetics
Epilepsy genetics
Megalencephaly genetics
PTEN Phosphohydrolase genetics
Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2350
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- BMC medical genetics
- Publication Type :
- Academic Journal
- Accession number :
- 24580998
- Full Text :
- https://doi.org/10.1186/1471-2350-15-26