Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.

Comparative analyses have identified genomic regions potentially involved in human evolution but do not directly assess function. Human accelerated regions (HARs) represent conserved genomic loci with elevated divergence in humans. If some HARs regulate human-specific social and behavioral traits, then mutations would likely impact cognitive and social disorders.

Using whole-exome sequencing to identify inherited causes of autism.

Despite significant heritability of autism spectrum disorders (ASDs), their extreme genetic heterogeneity has proven challenging for gene discovery. Studies of primarily simplex families have implicated de novo copy number changes and point mutations, but are not optimally designed to identify inherited risk alleles. We apply whole-exome sequencing (WES) to ASD families enriched for inherited causes due to consanguinity and find familial ASD associated with biallelic mutations in disease genes (AMT, PEX7, SYNE1, VPS13B, PAH, and POMGNT1).

Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected].

Genes disrupted in human microcephaly (meaning "small brain") define key regulators of neural progenitor proliferation and cell-fate specification. In comparison, genes mutated in human lissencephaly (lissos means smooth and cephalos means brain) highlight critical regulators of neuronal migration. Here, we report two families with extreme microcephaly and grossly simplified cortical gyral structure, a condition referred to as microlissencephaly, and show that they carry homozygous frameshift mutations in NDE1, which encodes a multidomain protein that localizes to the centrosome and mitotic spindle poles.

Identifying autism loci and genes by tracing recent shared ancestry.

To find inherited causes of autism-spectrum disorders, we studied families in which parents share ancestors, enhancing the role of inherited factors. We mapped several loci, some containing large, inherited, homozygous deletions that are likely mutations. The largest deletions implicated genes, including PCDH10 (protocadherin 10) and DIA1 (deleted in autism1, or c3orf58), whose level of expression changes in response to neuronal activity, a marker of genes involved in synaptic changes that underlie learning.

Transient nonketotic hyperglycinemia and defective serotonin metabolism in a child with neonatal seizures.

Neonatal nonketotic hyperglycinemia is usually fatal or, less commonly, severely developmentally disabling, whereas transient nonketotic hyperglycinemia has usually been followed by normal development. We report a boy who had transient neonatal nonketotic hyperglycinemia but a coexistent disorder of serotonin metabolism manifested by initially low cerebrospinal fluid 5-hydroxyindoleacetic acid (which later normalized), low whole blood serotonin, and decreased platelet serotonin uptake. He survived the neonatal period but was neurodevelopmentally delayed and developed an autistic-like disorder.

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome.

Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.

Randomized treatment study of inosiplex versus combined inosiplex and intraventricular interferon-alpha in subacute sclerosing panencephalitis (SSPE): international multicenter study.

The efficacy of oral inosiplex alone (group A) versus combined treatment of inosiplex (Isoprinosine) and intraventricular interferon-alpha2b (Intron A) (group B) in patients with subacute sclerosing panencephalitis (SSPE) was compared. One hundred and twenty-one patients who met the diagnostic criteria for subacute sclerosing panencephalitis and presented at stage 2 or less were randomized into group A or B. Data were analyzable on 67 patients who met the inclusion criteria and adhered to the protocol.

Supplementation with omega-3 polyunsaturated fatty acids in the management of recurrent migraines in adolescents.

Purpose: To examine whether dietary supplementation with fish oil rich in very long-chain n-3 polyunsaturated fatty acids might reduce frequency and severity of migraines in adolescents.

Methods: Twenty-seven adolescents suffering from frequent migraines for at least 1 year (mean 4 +/- 1 years since migraine onset) participated in a randomized, double-blind, cross-over study consisting of 2 months of fish oil, 1-month washout period, and 2 months of placebo (olive oil). Participants self-assessed severity and duration of headache episodes (7-point faces and 10-point visual analog pain scales, 5-point frequency and severity rating scale) throughout the study.