COL4A1-related autosomal recessive encephalopathy in 2 Turkish children.

OBJECTIVE: This study presents the neurologic phenotypes of 2 brothers with a novel homozygous COL4A1 mutation that was identified in a large Turkish consanguineous cohort of neurogenetic diseases. METHODS: Whole-exome sequencing and bioinformatic analysis of consanguineous families with children affected by early-onset, neurogenetic disorders was performed using the RD-Connect Genome-Phenome Analysis Platform. We also performed clinical, EEG, and neuroimaging analyses in unaffected siblings and parents. RESULTS: We have identified a homozygous missense mutation in COL4A1 (p.Gly1278Ser, NM_001845.5:c.3832G>T) in 2 siblings affected by small vessel brain disease with periventricular leukoencephalopathy and ocular defects. Presenting symptoms included mild weakness, hemiparetic gait, pyramidal findings, and seizures, whereas their intellectual and behavioral functions were normal. Both parents and 5 of the siblings (3 boys and 2 girls) were heterozygous for the variant. They did not show any clinical or laboratory signs of small vessel disease. CONCLUSIONS: COL4A1 has previously been associated with dominant small vessel disease of the brain and other organs, manifesting with high penetrance in heterozygous mutation carriers. Our findings provide evidence that COL4A1-related encephalopathy can be inherited in an autosomal recessive manner, which is important for counseling, prognosis, and treatment. Genotype-phenotype correlations remain to be established.

Cerebellar volume in early-onset schizophrenia and its association with severity of symptoms.

OBJECTIVES: This study aimed to investigate whether early-onset schizophrenia (EOS) cases differ from controls regarding volumes of the total cerebellum and the right and left cerebellar hemispheres, and volumetric asymmetry. Correlations of cerebellar volumes and asymmetry indices with severity of symptoms and general functioning in cases of EOS were also assessed. METHODS: Adolescents with EOS (n = 23) were compared with controls (n = 23). Sociodemographic and clinical data, and magnetic resonance imaging scans that were acquired for routine clinical purposes were collected retrospectively. Cerebellar volumes were evaluated using the stereological method. Asymmetry indices were subsequently calculated. Scores of the Positive and Negative Syndrome Scale and the Children's Global Assessment Scale were used to assess the severity of symptoms and general functionality. RESULTS: There were no significant differences in any of the cerebellar volumes and asymmetry indices between the two groups. Neither cerebellar volumes nor asymmetry indices were correlated with the severity of symptoms and general functionality in EOS. CONCLUSIONS: Our findings suggest that the early-onset form of schizophrenia does not show apparent volumetric changes of the cerebellum. Additionally, the neural circuits involved in formation of symptomatology may not reflect any correlation with cerebellar volumes at mid-adolescence.