DIA1R Is an X-Linked Gene Related to Deleted In Autism-1

Background: Autism spectrum disorders (ASDs) are frequently occurring disorders diagnosed by deficits in three core functional areas: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. Methodology/Principal Findings: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62 % similar overall (28 % identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. Conclusions/Significance: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-lik

Partial seizures with focal epileptogenic electroencephalographic patterns in three related female patients with fragile-X syndrome

Epilepsy and abnormal electroencephalographic (EEG) patterns have been reported in mentally retarded males with fragile-X syndrome, but the high incidence of epilepsy in such persons has been recognized only recently. These individuals have focal spikes in the EEG similar to the benign rolandic pattern. Female carriers have very rarely been reported to have epilepsy or nonspecific abnormal EEG patterns. We report partial seizures with a focal epileptogenic EEG pattern in two sisters and their grandmother, who are all carriers of fragile-X syndrome. The sisters have mild developmental delay, but the grandmother is of normal intelligence. The mother of the two sisters is known to be a carrier of the fragile-X chromosome and is of normal intelligence, with no history of seizures. It is important for physicians to be aware of the possibility that females presenting with partial seizures of unknown cause may be fragile-X carriers, and enquiry for a family history of intellectual disability should be pursued.Rita Singh, Grant R. Sutherland, and James Manso