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Am J Med Genet B Neuropsychiatr Genet. 2012 Apr;159B(3):354-8. doi: 10.1002/ajmg.b.32036. Epub 2012 Feb 15.

Mutations in NRXN1 in a family multiply affected with brain disorders: NRXN1 mutations and brain disorders.

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  • 1Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.


Mutation of the neurexin1-gene, NRXN1, interrupting the expression of neurexin1 has been associated with schizophrenia, autism, and intellectual disability. We have identified a family multiply affected with psychiatric, neurological, and somatic disorders along with an intricate co-segregation of NRXN1 mutations. The proband suffered from autism, mental retardation, and epilepsy and on genotyping it was revealed that he carried a compound heterozygous mutation in the NRXN1 consisting of a 451 kb deletion, affecting the promoter and first introns in addition to a point mutation, predicted to be deleterious to NRXN1. The deletion was passed on from the patient's mother who was clinically characterized by sub-diagnostic autistic traits in addition to type 1 diabetes mellitus. The point mutation was subsequently found in the patient's brother, suffering from a psychotic disorder, which implies that the point mutation was inherited from the deceased father, who was diagnosed with schizophrenia. The observations suggest a possible gene-dose effect of NRXN1 mutations on type and severity of mental illness and support the notion that the penetrance and pleiotropy of pathogenic CNVs in general are determined by additional genetic variants in the genome. Finally the findings also propose a linkage of NRXN1 neurobiology to epilepsy and possibly to type 1 diabetes.

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