Neuropsychiatric phenotype in relation to gene variants in the hemizygous allele in 3q29 deletion carriers: A case series

• Main Authors: Eva Albertsen Malt, Katalin Juhasz, Anna Frengen, Teresia Wangensteen, Nina Merete Emilsen, Borre Hansen, Oleg Agafonov, Hilde Loge Nilsen
• Format: Article
• Language: English
• Published: Wiley 2019-09-01
• Series: Molecular Genetics & Genomic Medicine
• Subjects: 3q29 deletion; autistic disorder; cilia; schizophrenia; synaptic function
• Online Access: https://doi.org/10.1002/mgg3.889

Abstract Background Genetic risk variants in the hemizygous allele may influence neuropsychiatric manifestations and clinical course in 3q29 deletion carriers. Methods In‐depth phenotypic assessment in two deletion carriers included medical records, medical, genetic, psychiatric and neuropsychological evaluations, brain MRI scan and EEG. Blood samples were analyzed for copy number variations, and deep sequencing of the affected 3q29 region was performed in patients and seven first‐degree relatives. Risk variants were identified through bioinformatic analysis. Results One deletion carrier was diagnosed with learning difficulties and childhood autism, the other with mild intellectual disability and schizophrenia. EEG abnormalities in childhood normalized in adulthood in both. Cognitive abilities improved during adolescence in one deletion carrier. Both had microcytic, hypochromic erythrocytes and suffered from chronic pain and fatigue. Molecular and bioinformatic analyses identified risk variants in the hemizygous allele that were not present in the homozygous state in relatives in genes involved in cilia function and insulin action in the autistic individual and in synaptic function and neurosteroid transport in the subject with schizophrenia. Conclusion 3q29 deletion carriers may undergo developmental phenotypic transition and need regular medical follow‐up. Identified risk variants in the remaining hemizygous allele should be explored further in autism and schizophrenia research.